The review’s abstract describes recent progress in identifying novel Cas orthologs and engineering Cas9 variants to improve editing fidelity, expand target ranges and reduce off-target effects. It also reports that structural and functional optimization of single-guide RNAs has improved target-binding affinity, stability and formation of the Cas9-sgRNA complex. High-fidelity Cas9 derivatives, base editors and prime editors are presented as enabling precise single-nucleotide substitutions and small insertions or deletions without producing double-stranded DNA breaks.

Delivery remains a central focus. According to the abstract, viral vectors, lipid nanoparticles and ribonucleoprotein electroporation have advanced CRISPR-mediated editing across in vitro, ex vivo and in vivo models. The review highlights therapeutic milestones reported for sickle cell disease, β-thalassemia and cystic fibrosis, where the abstract states that long-term clinical benefits have been documented. It also identifies a separate research role for CRISPR-Cas9 in diabetes: modeling disease mechanisms, identifying molecular pathways involved in glucose homeostasis and supporting development of cellular and gene-based therapies.

This is a review rather than a new clinical trial, laboratory study or protocol, and the available evidence consists of the article’s abstract and publisher information rather than the full text. The abstract does not provide study populations, sample sizes, quantitative editing efficiencies, delivery-performance measures, follow-up periods, safety outcomes or a systematic assessment of the cited clinical evidence. Consequently, the reported therapeutic milestones and broader translational claims are summarized here as the review’s conclusions; the available source does not support independent verification of their magnitude or applicability to individual patients.

Subject of Research: CRISPR-Cas9 genome editing technologies, delivery systems and therapeutic applications

Article Title: CRISPR–Cas9 genome editing: technological advances, delivery strategies and precision engineering of primary cells for therapeutic application in genetic disorders and diabetes mellitus

Article References: Islam, M. N., Islam, M. M., Feng, H., Bellah, S. F., Zaman Miah, M. M., & Hossain, M. S. (2026). CRISPR–Cas9 genome editing: technological advances, delivery strategies and precision engineering of primary cells for therapeutic application in genetic disorders and diabetes mellitus. Molecular Biology Reports, 53(1), Article 1589. https://doi.org/10.1007/s11033-026-12771-1

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12771-1

Keywords: CRISPR-Cas9, genome editing, base editing, prime editing, gene delivery, primary cells, genetic disorders, sickle cell disease, β-thalassemia, cystic fibrosis, diabetes mellitus, CRISPR

Irreversible electroporation, or IRE, is not a new idea. The technique uses high-voltage, low-energy electrical pulses delivered between thin needle electrodes to punch permanent nanoscale pores into cell membranes. Once membrane integrity is irreversibly lost, cells die through apoptotic and necrotic pathways rather than through the heat-driven protein denaturation that characterizes radiofrequency or laser ablation. Because tissue destruction is electrical rather than thermal, the scaffolding of the tissue—the extracellular matrix, blood vessels, and nerves—largely survives. That property has made IRE attractive for treating tumors in organs such as the liver, pancreas, and prostate, where preserving surrounding structures matters enormously.

Conventional IRE, however, has an uncomfortable side effect. The unipolar pulses it employs are strong enough to stimulate nerves and muscles, producing dramatic whole-body contractions that typically require deep anesthesia and neuromuscular blockade. High-frequency irreversible electroporation, known as H-FIRE, addressed this by delivering ultra-short bipolar pulses that fall within the refractory period of nerve cells, keeping stimulation below the threshold for action potentials. Preclinical and early clinical studies of H-FIRE in prostate ablation have confirmed effective lesion formation with markedly reduced muscle contraction. But most of these studies relied on fixed waveform structures or single pulse widths, leaving open whether a smarter pulse recipe could do better.

The team behind the new work, based at Shanghai Municipal Hospital of Traditional Chinese Medicine and Shanghai Nortion Medical Technology, developed a device that generates what they call highly heavy-frequency bipolar compound steep pulses. Their hypothesis was simple but consequential: if pulses of different durations and field strengths interact with tissue in complementary ways, combining them in a single ablation sequence should permeabilize a broader population of cells than any single waveform could. The device has passed registration testing at the Shanghai Testing and Inspection Institute for Medical Devices and is cleared for clinical trials, making this canine study a critical preclinical stepping stone.

The experiment was designed as a sequential, stepwise parameter optimization. Each of the twenty Beagles contributed two prostate lobes, giving forty treatment sites and reducing the number of animals required. In the first phase, escalating voltages established safe operating ranges: with 5-microsecond pulses, voltages up to 2500 volts produced muscle contractions graded at most as moderate, while 50-microsecond pulses remained acceptable up to 1500 volts. In the second phase, the researchers compared single-pulse and compound-pulse protocols head to head under identical electrode placement. The results were unambiguous. A 5-microsecond pulse at 1500 V/cm ablated 39.30 square millimeters of tissue; a 50-microsecond pulse at 1000 V/cm managed 64.44 square millimeters. The compound protocol—both pulses in sequence—carved out 307.27 square millimeters, roughly five to eight times the area of either single-pulse approach.

The third phase systematically varied electric-field strength, interelectrode spacing, and insertion depth. Mean ablation areas in the low-, medium-, and high-parameter groups were 39.74, 175.46, and 228.49 square millimeters, respectively. The medium and high groups both significantly outperformed the low group, but the difference between medium and high was not statistically significant. Crucially, the high-parameter group produced significantly greater muscle contraction than the medium group. The authors interpret this through the sigmoidal dose-response characteristic of electroporation: once the tissue-specific ablation threshold—estimated at roughly 1072 V/cm for canine prostate—is exceeded, pushing the field higher adds little therapeutic benefit but preferentially amplifies neuromuscular stimulation, since nerve and muscle excitation thresholds sit far below the ablation threshold.

Electrode geometry proved equally important. At spacings of 10, 14, and 18 millimeters, mean ablation areas were 83.93, 226.25, and 216.20 square millimeters. The 14-millimeter configuration delivered the largest lesion, and the researchers conclude that the practical spacing window lies between 14 and 18 millimeters rather than at a single optimum. Increasing insertion depth from 10 to 20 millimeters, by contrast, yielded only a modest gain—from 83.93 to 90.10 square millimeters—suggesting that cross-sectional lesion size is governed more by electrode spacing than by how deep the needles sit within the gland.

Safety findings were reassuring across the seven-day follow-up. No serious adverse events occurred, wounds healed without complication, and gross prostate appearance remained normal. Red blood cell counts, hemoglobin, and platelets showed no clinically relevant changes relative to published reference change values for laboratory Beagles. White blood cell counts rose transiently after the procedure, a pattern the authors attribute to surgical stress and the localized inflammatory response that follows tissue injury rather than systemic toxicity. Only one dog showed a leukocyte increase exceeding the reference change value, consistent with a more pronounced inflammatory reaction.

The mechanism behind the compound-pulse advantage remains an open question, though a plausible model has emerged from earlier work in potato tubers, rabbit liver, mouse tumors, and porcine liver. High-voltage narrow pulses can perforate cell membranes, but those perforations often reseal without killing the cell. A subsequent lower-voltage, broader pulse may widen these transient pores past the point of recovery, pushing cells into irreversible death. In effect, the two waveforms act as a one-two punch: the first creates the vulnerability, the second exploits it. The authors caution that this synergy was not directly tested in prostate tissue and that impedance measurements and computational field modeling will be needed to confirm it.

Limitations temper the enthusiasm appropriately. The study was conducted in healthy canine prostates, which may not fully mirror the electrical and tissue properties of human benign or malignant prostate disease. Each parameter configuration was evaluated in only three prostate lobes, and the reported field strengths represent device output settings rather than measured tissue distributions. Adjacent critical structures such as the urethra were preserved histologically but not systematically evaluated, and longer follow-up with electromyography will be needed to fully characterize neuromuscular responses. Still, the core conclusion stands: the medium-parameter compound protocol—5-microsecond pulses at 1500 V/cm combined with 50-microsecond pulses at 1000 V/cm—achieved a favorable balance between ablation area and muscle contraction, and no serious adverse events emerged. As the first systematic parameter optimization of compound steep-pulse ablation in a large-animal prostate model, the study lays the quantitative groundwork for the clinical trials that must follow before this technology reaches patients with benign prostatic hyperplasia or prostate cancer.

Subject of Research: Compound steep-pulse irreversible electroporation for prostate ablation in Beagle dogs: parameter evaluation and short-term safety

Article Title: Compound steep-pulse irreversible electroporation for prostate ablation in Beagle dogs: parameter evaluation and short-term safety

Article References: Chen, Z., Zhao, L., Zhang, Z., & Luo, Z. (2026). Compound steep-pulse irreversible electroporation for prostate ablation in Beagle dogs: parameter evaluation and short-term safety. Frontiers in Urology, 6, Article 1721078. https://doi.org/10.3389/fruro.2026.1721078

Image Credits: AI Generated

DOI: 10.3389/fruro.2026.1721078

Keywords: Compound, steep-pulse, irreversible, electroporation, prostate, ablation, Beagle, dogs, parameter, evaluation, short-term, safety

The motivation is straightforward. Hazelnut is a high-value perennial nut crop, with global production concentrated in Turkey and Italy and expanding in the United States and Chile. In Oregon’s Willamette Valley, hazelnut supports many growers and rural communities and supplies a key raw ingredient for confectionery products, including chocolate-based goods. But weed management in hazelnut orchards is a persistent challenge. Tree rows are permanent, mechanical access is limited because cultivation can damage the shallow root system, and weeds compete with young trees, reducing growth, productivity, and long-term orchard performance. Effective in-row weed control during the first years after planting is critical for rapid canopy development and for maintaining the clean orchard floor required for efficient nut harvest.

That challenge has traditionally been met with repeated herbicide applications in the planted row combined with flail mowing the alleyways. Continued reliance on herbicides intensifies selection pressure for resistant weed populations, and in Oregon hazelnut orchards, herbicide-resistant weeds have already been documented, including Italian ryegrass and annual bluegrass. Recent work has identified multiple herbicide-resistance cases in annual bluegrass, underscoring how vulnerable perennial orchard systems are to resistance evolution under repeated chemical applications. The search for nonchemical tools capable of diversifying weed management programs has therefore become urgent.

Electric weed control is one promising area, but most existing systems deliver energy to weed foliage. In aboveground contact systems, electrodes touch plant tissues, allowing current to pass through the weed and into the soil. Electricity flowing through the plant increases tissue temperature, disrupts cellular integrity, and can result in plant death. These systems are generally most effective on young, herbaceous, and well-hydrated weeds, but they can be bulky, energy-demanding, and nonselective, requiring careful application to avoid crop injury. PEF differs from these alternating-current systems because it delivers short, high field-strength electrical pulses rather than continuous energy. The pulses disrupt cellular membranes through electroporation, a process in which an external electric field destabilizes the lipid bilayer. When the induced membrane disruption is temporary, cells may recover; when it is severe or prolonged, electroporation becomes irreversible, leading to loss of membrane function, cellular leakage, and tissue death.

Soil-applied PEF goes one step further: instead of contacting weed foliage, electrodes are inserted into the soil or placed on opposite sides of a defined soil volume, and short electrical pulses are discharged between electrodes of opposite polarity. Current moves through conductive soil-water pathways, and biological targets are exposed when seeds, propagules, roots, or emerging seedlings intersect the effective electric field. Previous work has shown that soil-applied PEF can suppress plant-parasitic nematodes and soilborne pathogens, suggesting that a lethal electrical dose can be delivered to below-ground targets. From a biological perspective, germinating weed seeds and vegetative propagules may be particularly suitable targets because germination activates membrane systems, increases tissue hydration, and establishes conductive plant-soil pathways that facilitate current flow through living tissues. Electroporation theory predicts that metabolically active cells are more susceptible to irreversible membrane destabilization when critical transmembrane potentials are reached.

The Oregon team, led by Pamela Medeiros dos Santos, Tatiana Benedetti, and Marcelo L. Moretti, evaluated soil-applied PEF in a six-month-old experimental hazelnut orchard at the Lewis-Brown Research Farm near Corvallis, on a Malabon silty clay loam with 5 percent organic matter. Treatments included a nontreated control, a hand-weeded control, and soil-applied PEF at 1, 10, and 100 joules per cubic centimeter, applied once in July 2025 using a vertical-pin soil electrode system that generated millisecond-duration pulses at a field strength of 200 volts per millimeter. The stationary electrode frame consisted of two rows of 12 pins of positive and negative polarity, spaced 30 centimeters apart, treating a 60-centimeter swath and an estimated soil volume of approximately 0.018 cubic meters per placement. Weed control was assessed visually up to 60 days after treatment, and crop response was evaluated through visual injury ratings and physiological measurements, including leaf chlorophyll content, photosystem II quantum efficiency, and stomatal conductance.

The field results were sobering for weed control but reassuring for the trees. PEF at 1 and 10 joules per cubic centimeter produced 0 percent weed control at every assessment, indistinguishable from the nontreated control. The highest energy density, 100 joules per cubic centimeter, produced minor numerical suppression, reaching 25 percent visual weed control at 1 and 3 days after treatment, but this response was not statistically different from the nontreated control and declined to below 13 percent at 30 and 60 days. Only hand weeding controlled weeds, primarily yellow nutsedge, consistently reaching 100 percent across all evaluation dates. Crop injury, by contrast, was negligible throughout the study. Injury ratings were 0 percent for the control, hand-weeding, and the lowest PEF treatment at all evaluation dates, with only 2.5 percent injury observed later in the season for the two highest energy treatments. Physiological measurements showed no consistent treatment effects over time; chlorophyll content increased as leaves matured, photosystem II efficiency remained similar across treatments, and stomatal conductance increased quickly after treatment and then remained within a similar range among treatments through 60 days. The temporal variation was likely driven by seasonal and environmental factors rather than the electrical treatment itself.

In parallel greenhouse experiments, the researchers planted tubers of yellow nutsedge and seeds of barnyard grass and Palmer amaranth in containers and incubated them in moist soil for 0, 3, 5, or 7 days before applying PEF at 0, 25, 50, or 200 joules per cubic centimeter using a parallel-plate applicator. One aluminum electrode was placed at the bottom of the container before filling with soil, and a second was placed on the soil surface with a spring-loaded mechanism ensuring consistent contact, forcing current vertically through the entire soil column. Plants were harvested 28 days after treatment, and shoots and roots were separated, dried, and weighed. Redundancy analysis indicated that, after accounting for species effects, energy density and incubation time explained a small but significant portion of the multivariate variation in biomass, with incubation time the strongest experimental predictor, followed by energy density. Species identity accounted for the majority of total variation in biomass response.

The species-specific results were striking. Yellow nutsedge tubers exhibited the greatest biomass and the strongest response to PEF: treatments substantially reduced shoot and root biomass at 3, 5, and 7 days after planting, often approaching zero regardless of energy density. Slope analysis showed strong negative relationships between incubation time and biomass at 25 and 50 joules per cubic centimeter, with shoot and root biomass declining by roughly 0.098 and 0.174 to 0.179 grams per day, respectively, indicating a pronounced increase in susceptibility with delayed exposure. At 200 joules per cubic centimeter, no clear incubation-time effect was observed, suggesting this energy density was sufficient to cause high levels of control regardless of tuber developmental stage. Palmer amaranth showed a significant negative relationship between incubation time and biomass at 50 joules per cubic centimeter for both shoots and roots, while barnyard grass biomass declined with increasing incubation time at 0 and 25 joules per cubic centimeter for shoots, though the magnitude of the response was smaller and less consistent across energy densities. Across species, increasing incubation time generally enhanced PEF efficacy, particularly at intermediate energy densities, indicating that delayed application coinciding with early seedling development increased treatment effectiveness.

The contrasting responses between field and container studies were likely driven by differences in applicator configuration, treated soil volume, and electric field distribution. The vertical-pin configuration used in the orchard treated a larger and more heterogeneous soil volume, where soil moisture, bulk density, organic matter, roots, and weed position likely altered current pathways. Because electric current follows the path of least resistance, portions of the treated soil volume may have received sublethal exposure, with localized regions of high intensity near electrodes and large portions of the treated volume receiving sublethal doses. The transient weed suppression observed at 100 joules per cubic centimeter may also reflect incidental direct contact between the applicator and weed foliage rather than an effect of electricity moving through the soil to the roots. In contrast, the parallel-plate configuration directed current vertically through a smaller, more uniform soil column, increasing electrode contact area and improving the likelihood that germinating seeds, tubers, roots, and emerging shoots intersected the effective electric field. The difference in energy range should also be considered, as the container experiment included 200 joules per cubic centimeter while the highest field energy was 100; greater field suppression might have occurred at higher energy densities, though increasing energy in field soil would also raise energy demand and may reduce field-scale practicality unless energy delivery becomes more targeted and efficient.

The timing effect has a clear physical explanation. As seeds imbibe water and tissues differentiate, dielectric constant and electrical conductivity increase, facilitating current flow through plant tissues. Previous studies have shown that conductivity in germinating seeds increases several-fold as water content and tissue connectivity increase; in seeds of Cardiospermum halicacabum, conductivity remained low during early imbibition but increased approximately 5 to 10 times between days 7 and 14 of germination, and in snap bean, increasing seed moisture content from approximately 25 to 50 percent resulted in substantial increases in conductivity and corresponding reductions in electrical resistance. In the present study, weed propagules incubated in soil for 3 to 5 days were generally the most affected, aligning with the idea that developing seedlings provide more continuous conductive pathways for the electrical current. Ungerminated propagules were less affected at lower energies, likely due to limited conductive pathways. Species-specific responses were also expected, as differences in seed size, morphology, and early growth patterns influence the formation of conductive pathways and recovery potential following injury.

Scalability remains a major limitation for soil-applied PEF in orchard systems. Energy treatments were expressed as nominal applied energy density, but real-time operational energy consumption, equipment efficiency, duty cycle, treatment speed, and field work rate were not measured, so field-scale energy requirements cannot be fully estimated from these data. Actual orchard energy demand would depend on treated band width, electrode geometry, soil moisture, soil electrical conductivity, contact efficiency, and the proportion of orchard floor treated. These limitations suggest that soil-applied PEF may be better suited for targeted applications, such as localized treatment of persistent weed patches or belowground pest targets, rather than broadcast treatment of large soil volumes. Alternatively, future development may need to explore other electricity-delivery pathways, including foliar application, where direct contact with aboveground weed tissues may improve energy-use efficiency and biological response.

Overall, the primary limitation of soil-applied PEF for weed control is not necessarily the biological sensitivity of weeds but the ability to deliver sufficient and uniform energy under field conditions. The container study demonstrates that growth suppression is achievable when exposure is uniform, whereas the orchard study shows that a single soil application with the vertical-pin configuration did not provide consistent weed control. Improving field efficacy will likely require application strategies that increase the probability of current passing through target tissues, including modified electrode designs, repeated applications to compensate for variability in contact, or integration with other nonchemical approaches. The high level of crop safety observed also supports further exploration of soil-applied PEF for belowground targets. Although soil-applied PEF was ineffective for weed control under the orchard conditions tested, it may become a viable component of integrated weed management in perennial horticultural systems if energy delivery and biological targeting are better aligned. The research was supported by the USDA National Institute of Food and Agriculture through the Crop Protection and Pest Management Program, with additional support from the Oregon Hazelnut Commission and Ferrero Hazelnut Company.

Subject of Research: Agricultural Science

Article Title: Hazelnut tolerance and weed response to soil-applied pulsed electric field

Article References: Medeiros dos Santos, P., Benedetti, T., & Moretti, M. L. (2026). Hazelnut tolerance and weed response to soil-applied pulsed electric field. Frontiers in Horticulture, 5, Article 1833896. https://doi.org/10.3389/fhort.2026.1833896

Image Credits: AI Generated

DOI: 10.3389/fhort.2026.1833896

Keywords: pulsed electric field, PEF, weed control, hazelnut, electroporation, nonchemical weed management, orchard systems, soil-applied technology, herbicide resistance, sustainable agriculture, tolerance, weed

The appeal of PEF lies in what it avoids. Conventional pasteurization of fruit and vegetable juices relies on intense heat, which effectively eliminates pathogens and spoilage organisms but simultaneously degrades vitamins, polyphenols, flavonoids, and carotenoids, the very compounds that make juices attractive to health-conscious consumers. PEF works differently. When microbial cells are exposed to an electric field strength above roughly 10 kV/cm for micro- to millisecond durations, a phenomenon called electroporation occurs: the cell membrane, normally an insulating barrier, develops pores as the transmembrane potential exceeds a critical threshold. If the pores reseal, the cell survives, injured but alive. If they fail to reseal, the cell dies. The new study tackles both outcomes head-on, quantifying not just how many cells die but how many are left in that dangerous middle state of sub-lethal injury.

The experimental setup was deliberately designed to mimic industrial conditions. The team used a continuous-flow PEF system, the EPULSUS-BM1A-12 pulse generator, pumping juice at 6 liters per hour through a treatment chamber with parallel titanium electrodes separated by a 0.4-centimeter gap. Square-wave pulses of 4 microseconds were applied at a field strength of 20 kV/cm, with repetition frequencies ranging from 4 to 78 Hz. This produced treatment times between 0 and 112.3 microseconds and total specific energies from 0 up to 139.2 kJ/kg, with outlet temperatures held between 20 and 55.8 degrees Celsius, well below what conventional pasteurization would require. Three juices with sharply different chemistries served as the test matrices: acidic pomegranate juice at pH 3.1, moderately acidic tomato juice at pH 4.4, and nearly neutral carrot juice at pH 6.1, each with distinct conductivity and soluble solids content.

Four microbial strains were put through this gauntlet: two strains of Escherichia coli, the laboratory strain K12 and the foodborne isolate FAM 21843 originally recovered from raw milk cheese, and two strains of the spoilage yeast Saccharomyces cerevisiae, AD1890 isolated from fruit and 130.0014 from the food industry. The results met and in some cases exceeded the benchmark that matters most for commercialization. The U.S. Food and Drug Administration requires a 5-log reduction, meaning a 100,000-fold decrease in the most resistant foodborne pathogen, before PEF can be approved for commercial juice pasteurization. In pomegranate and carrot juices, both E. coli strains achieved greater than 5-log reductions at the highest treatment intensities. Tomato juice proved more challenging, yielding reductions above 3.85 logs, a shortfall the authors attribute to its intermediate acidity and composition.

One of the most technically important aspects of the study is its modeling approach. Traditional kinetic modeling proceeds in two stages: a primary model is fitted to each survival curve individually, and then the resulting parameters are linked to process variables through a secondary model. This stepwise procedure propagates errors and wastes information. Instead, the researchers fitted primary and secondary models simultaneously to the full dataset, combining a log-linear primary model with a second-order polynomial secondary model that describes how the maximum specific inactivation rate, k-max, depends on total specific energy. The polynomial captures three things at once: a baseline inactivation constant C1, a linear sensitivity coefficient C2, and a quadratic coefficient C3 that accounts for nonlinear acceleration or deceleration of killing as energy accumulates. Model performance was excellent, with regression coefficients ranging from 0.965 to 0.998 across all twelve strain-juice combinations.

The survival curves themselves were anything but the simple straight lines that early PEF studies reported. Those earlier log-linear observations, the authors note, likely reflected limited inactivation levels below 4 logs achieved at low field strengths or short durations. At the intensities tested here, the curves were distinctly multiphasic. In pomegranate juice, the E. coli strains showed concave downward kinetics, a slow initial decline that accelerated sharply after 47.12 microseconds of treatment. In carrot juice, the pattern inverted: a pronounced shoulder of resistance persisted up to about 44.64 microseconds, followed by a rapid collapse in viability beyond 61.92 microseconds. Tomato juice produced near log-linear behavior with slight tailing. The yeast strains followed similar matrix-dependent patterns, with S. cerevisiae showing particularly sharp sensitivity in tomato juice beyond 38.48 microseconds of treatment.

Statistical analysis of the fitted parameters revealed a satisfying hierarchy of effects. The linear coefficient C2 did not differ significantly across any strain or juice, suggesting a conserved, universal linear response of microbial populations to increasing energy input. In contrast, the baseline inactivation constant C1 and the quadratic coefficient C3 both varied significantly, clustering strains into distinct statistical groups. E. coli K12 in pomegranate juice showed one of the highest baseline inactivation rates, while S. cerevisiae 130.0014 in carrot juice showed the lowest. Notably, E. coli FAM 21843 displayed no matrix dependence in its baseline rate, meaning its initial susceptibility to PEF was unaffected by which juice it was suspended in. The predicted inactivation rates climbed steeply for all strains at total specific energies above 80 kJ/kg, with S. cerevisiae 130.0014 showing the highest rate at high energies in pomegranate and tomato juices, marking it as the most energy-sensitive organism tested.

Strain heterogeneity, the bane of predictive food microbiology, showed up in the details. The two E. coli strains behaved nearly identically across all juices, with one exception: in the most acidic matrix, pomegranate juice, FAM 21843 proved more resistant than K12, showing a 1.71-log reduction versus K12’s 2.36-log reduction at 72.32 kJ/kg. Among the yeasts, AD1890 was consistently more resistant than 130.0014 at high energy levels, a pattern that echoes earlier findings from the same laboratories under high-pressure processing and ultrasound, hinting at cross-resistance to multiple preservation stresses in the AD1890 strain. Sub-lethal injury, assessed by plating on selective versus nonselective media, was minimal in tomato and carrot juices but pronounced in pomegranate juice at medium energy levels, where the gap between counts on the two media widened, indicating a pool of membrane-damaged cells that could potentially recover during storage.

Crucially for consumers, the treatment left the juices’ nutritional chemistry untouched. Measurements of total phenolic content, total flavonoid content, total orthodiphenol content, and CUPRAC antioxidant capacity showed no statistically significant differences between untreated and PEF-treated samples for any of the three juices. This aligns with prior reports that PEF preserves anthocyanins in pomegranate juice, carotenoids in tomato juice, and antioxidant capacity in carrot juice, sometimes through twelve weeks of refrigerated storage. The combination of FDA-relevant microbial reductions and intact bioactive compounds is precisely the value proposition that has kept PEF on the industry’s wish list for decades.

The study’s authors are candid about what remains to be done. Future models should explicitly account for strain and matrix variability, other quality attributes such as color, volatile compounds, and flavor deserve investigation, and the capital cost of PEF equipment remains a significant barrier to widespread adoption. But the message of this work is clear and commercially resonant: under realistic continuous-flow conditions, total specific energy is the master variable controlling microbial inactivation by PEF, a well-fitted polynomial model can predict it across organisms and juices, and the technology can deliver pathogen-killing performance without sacrificing the antioxidants that sell fresh juice in the first place.

Subject of Research: Kinetic modeling of microbial inactivation in fruit and vegetable juices treated with pulsed electric fields

Article Title: Kinetic Modeling of Microbial Inactivation in Juices Treated With Pulsed Electric Fields (PEF): A Comparative Study on Microbial Heterogeneity and Food Matrix Effects

Article References: Lytras, F., Psakis, G., Xuereb, M., Lia, F., Gatt, R., Raso, J., & Valdramidis, V. (2026). Kinetic Modeling of Microbial Inactivation in Juices Treated With Pulsed Electric Fields ( PEF ): A Comparative Study on Microbial Heterogeneity and Food Matrix Effects. Food Science & Nutrition, 14(10), Article e72408. https://doi.org/10.1002/fsn3.72408

Image Credits: AI Generated

DOI: 10.1002/fsn3.72408

Keywords: pulsed electric fields, food safety, microbial inactivation, kinetic modeling, juice processing, electroporation, non-thermal processing, Escherichia coli, Saccharomyces cerevisiae, sublethal injury, antioxidants, food matrix effects

The central obstacle to studying proteins inside mitochondria has always been delivery combined with signal quality. In-cell NMR, a technique pioneered nearly two decades ago, allows researchers to observe isotopically labeled proteins inside living cells, but applying the same logic to a subcellular organelle is far harder. Mitochondria are small, bounded by a double membrane, and easily damaged during isolation. Earlier work, including a 2014 study by Barbieri, Luchinat and Banci, demonstrated that in-mitochondria NMR was conceptually possible, but the approach has remained technically demanding and limited in resolution. The new study, led by Conggang Li with co-first authors Zeting Zhang and Cai Zhang, builds on that foundation and pushes the method to the point where quantitative, atomic-resolution measurements become routine enough to answer biological questions.

The key innovation lies in sample preparation. The team delivers purified proteins directly into isolated mitochondria using electroporation, a technique in which brief electrical pulses create transient pores in membranes, allowing macromolecules to enter. Crucially, the researchers performed extensive control experiments to verify that the delivered proteins genuinely resided inside the organelles rather than clinging to the outer membrane or leaking into the surrounding buffer. By comparing NMR spectra of the mitochondrial samples with spectra of the supernatant after centrifugation, they confirmed that the signals they recorded arose from proteins within intact mitochondria. They also quantified the intramitochondrial concentration of each delivered protein by lysing the organelles after measurement and comparing integrated peak areas against an internal standard, a step that transforms the method from a qualitative observation into a genuinely quantitative tool.

Two complementary labeling strategies underpin the spectroscopy. For residue-resolved information, the team used uniformly nitrogen-15-enriched proteins and recorded two-dimensional proton-nitrogen correlation spectra, the workhorse experiment of solution NMR. Each cross-peak in such a spectrum corresponds to a specific atom pair in a specific amino acid residue, so changes in peak position, intensity or width report directly on what is happening to that part of the protein. In parallel, the researchers exploited fluorine-19 labeling, incorporating fluorinated amino acid analogues such as 3-fluorotyrosine and 5-fluorotryptophan into their target proteins. Fluorine-19 offers a background-free window into biological samples, because essentially no endogenous mitochondrial molecules contain fluorine, and modern fluorine probes, including the highly sensitive wPSP6F tag developed in the same laboratory, boost sensitivity further. Together, the two approaches allow the same molecular event to be viewed from complementary angles.

The biological centerpiece of the study is alpha-synuclein, the intrinsically disordered protein whose aggregation into Lewy bodies is a hallmark of Parkinson’s disease. Alpha-synuclein has long been suspected of interacting with mitochondrial membranes, particularly cardiolipin-rich regions of the inner membrane, and this interaction is thought to contribute to the mitochondrial dysfunction seen in the disease. Using their in-mitochondria NMR platform, the researchers observed how alpha-synuclein engages the mitochondrial membrane environment, with residue-resolved signal attenuation revealing which parts of the protein chain make contact with membranes. The spectra of nitrogen-15-enriched alpha-synuclein delivered into mitochondria isolated from rat liver and pig brain showed characteristic broadening and attenuation patterns that map the membrane-binding interface at single-residue resolution, something previously achievable only with simplified model membranes in a test tube.

Perhaps the most striking aspect of the work is its treatment of post-translational modifications, the chemical tags that cells attach to proteins to regulate their behavior. The team examined how modifications of alpha-synuclein, including phosphorylation and methionine oxidation, alter its interaction with the mitochondrial membrane. Oxidation is of particular interest because mitochondrial metabolism generates reactive oxygen species, and oxidized alpha-synuclein has been implicated in impaired clearance and altered chaperone binding. The researchers also probed how oxidized alpha-synuclein interacts with the mitochondrial chaperone TRAP1 and with protein disulfide isomerase, using methionine-selective nitrogen-15 enrichment to monitor the oxidation state directly. These experiments demonstrate that the platform can capture regulatory chemistry as it happens inside the organelle, not merely static structure.

To establish the generality of the method, the team turned to a well-characterized benchmark: the B1 domain of protein G, known as GB1, a small, stably folded globular protein that has served as a standard in NMR methodology development for years. By measuring GB1 inside mitochondria, the researchers could assess how the mitochondrial interior, with its crowded macromolecular environment, distinctive pH and high ionic strength, affects protein stability. They also engineered a GB1 variant and monitored its dimerization inside the organelle using fluorine-19 NMR, achieving quantitative insight into how the mitochondrial environment modulates protein-protein interactions. This matters because a growing body of evidence shows that the intracellular milieu, with its excluded-volume effects and specific weak interactions, can shift protein folding equilibria and binding affinities in ways that dilute buffer experiments cannot reproduce.

The technical rigor behind these measurements deserves emphasis. The team measured the internal pH of their mitochondrial preparations using the fluorescent dye BCECF and cross-checked it against NMR chemical shifts of alpha-synuclein, ensuring that spectral changes reflected genuine intramitochondrial conditions rather than artifacts of sample preparation. Deuterated GB1 was used to probe hydrogen exchange and protein dynamics inside the organelle, with time-resolved spectra showing how signals recover as amide protons exchange with solvent. Leakage controls, concentration quantification and comparisons between buffer and mitochondrial samples were performed for every protein studied, establishing a level of validation that will be essential if the method is to be adopted by other laboratories.

The implications extend well beyond method development. Mitochondrial dysfunction sits at the heart of Parkinson’s disease, Alzheimer’s disease, cardiomyopathy, diabetes and aging itself, yet most structural biology on mitochondrial proteins has been performed on purified components or membrane mimetics. A platform that reports on protein structure, stability and interactions inside intact mitochondria bridges the gap between reductionist test-tube biophysics and the messy reality of the organelle. It also complements other emerging approaches, such as dynamic nuclear polarization-supported solid-state NMR, which has recently been used to study nucleic acids and proteins in situ with subcellular specificity, and real-time NMR observations of endogenous cytochrome c translocation within mitochondria reported in 2024. Together these techniques sketch a future in which the atomic-resolution study of biology inside organelles becomes standard practice rather than a tour de force.

For the immediate future, the Wuhan team’s framework offers a template for exploring mitochondria-related biomolecular events that were previously out of reach: how disease-linked mutations change membrane binding, how chaperones protect proteins in the crowded mitochondrial interior, and how the organelle’s unique chemical environment reshapes the energy landscape of folding and aggregation. As the authors note, the approach paves the way toward a more comprehensive understanding of the molecular events governing mitochondrial health and dysfunction. If the method proves as adaptable as in-cell NMR in whole cells has been, the coming years could see atomic-resolution spectroscopy become a routine probe of the organelle whose failure underlies so much of human disease, finally letting researchers watch, atom by atom, what goes wrong inside the powerhouse.

Subject of Research: High-resolution NMR spectroscopy of proteins delivered into intact mitochondria

Article Title: High-resolution NMR spectroscopy of proteins in intact mitochondria

Article References: Zhang, Z., Zhang, C., Xu, G., Du, R., Yu, J., Liu, X., Chai, Z., Wu, Q., Jiang, L., Liu, M., & Li, C. (2026). High-resolution NMR spectroscopy of proteins in intact mitochondria. Nature Chemical Biology. https://doi.org/10.1038/s41589-026-02314-x

Image Credits: AI Generated

DOI: 10.1038/s41589-026-02314-x

Keywords: NMR spectroscopy, mitochondria, in-cell NMR, alpha-synuclein, Parkinson's disease, electroporation, fluorine-19 labeling, protein stability, post-translational modifications, mitochondrial membrane, structural biology, protein dimerization

Neuroblastoma is a cancer of the sympathetic nervous system that arises most often in the adrenal glands or along the spine, and it accounts for a disproportionate share of childhood cancer deaths. The girl at the center of this report carried one of the worst prognostic markers in the disease: amplification of the MYCN gene, a genetic signature associated with aggressive, treatment-resistant tumors. Her initial treatment followed the standard European induction protocol known as COJEC, a rapid cycle of cisplatin, vincristine, carboplatin, etoposide, and cyclophosphamide, followed by two courses of topotecan, vincristine, and doxorubicin. When doctors re-evaluated her disease, the news was grim. The primary tumor in her abdomen remained large and active, it pressed on critical blood vessels, and scans revealed widespread involvement of her bones and bone marrow, yielding a skeletal disease score of 45 on the SIOPEN scale used across European pediatric oncology centers.

What followed was a relentless escalation of therapy. Second-line chemotherapy with temozolomide and irinotecan, later combined with the anti-GD2 antibody dinutuximab beta, succeeded in clearing the metastatic disease from her bones and marrow. She then underwent consolidation with two rounds of radiometabolic therapy using iodine-131 labeled MIBG—a radioactive form of the same tracer molecule used to image neuroblastoma—each followed by reinfusion of her own stem cells, and finally high-dose chemotherapy with busulfan and melphalan supported by another stem-cell rescue. Yet when the dust settled, one enemy remained entrenched: a residual mass in her retroperitoneum, the space behind the abdominal organs, measuring 13.3 by 9.8 by 6.9 centimeters. The mass continued to light up on MIBG scans, proof that living neuroblastoma cells persisted within it, and it wrapped around the celiac artery and the right renal artery while compressing the inferior vena cava, the largest vein in the body.

This anatomical situation presented surgeons with an impossible calculus. Any attempt at resection risked catastrophic hemorrhage from vessels that the tumor had encased, and there was no guarantee that a complete removal could be achieved even at that price. A biopsy taken through the skin confirmed that the mass contained viable neuroblastoma tissue showing differentiating features, meaning the cells were still alive and capable of regrowth. It was at this impasse that a multidisciplinary tumor board—bringing together pediatric oncologists, surgeons, interventional radiologists, pathologists, and radiation therapists at Bambino Gesù Children’s Hospital in Rome—turned to a technique that had never before been applied to a child with this disease: percutaneous electrochemotherapy.

The principle behind electrochemotherapy is elegantly physical. Cell membranes, though thin, are formidable barriers that normally prevent many chemotherapy drugs from entering cells efficiently. When short, high-voltage electric pulses are applied across a tissue, they transiently reorganize the lipid bilayer of those membranes, opening nanoscale pores in a process called reversible electroporation. The pores allow drug molecules to flood into the cell interior, and because the pulses are calibrated carefully, the membranes reseal afterward and the cells survive—only to be killed by the chemotherapy they have now absorbed in quantities far beyond what ordinary exposure could achieve. The drugs most commonly paired with electroporation are bleomycin and cisplatin, both of which become dramatically more cytotoxic inside electroporated cells. In adults, the technique has earned validated roles against melanoma, sarcoma, and head and neck tumors, but pediatric experience has been almost nonexistent.

The Roman team tailored the procedure to the unique biology of neuroblastoma. Rather than administering cisplatin intravenously, they injected it directly into the tumor, a strategy designed to maximize drug concentration within the lesion while minimizing systemic side effects—a rational choice given that platinum compounds are among the drugs to which neuroblastoma is classically sensitive. Under general anesthesia, with the child positioned prone, three variable-geometry needle electrodes with an active length of three centimeters were inserted intercostally, between the ribs, using computed tomography and ultrasound guidance. The target was the most metabolically active portion of the mass, precisely the region where MIBG single-photon emission imaging had shown the greatest tracer uptake and where the tumor pressed hardest against the inferior vena cava. Once the electrodes bracketed the target, an 18-gauge coaxial biopsy was taken through the field, and four milligrams of cisplatin at a concentration of two milligrams per milliliter were injected through a Chiba needle. The Cliniporator VITAE device then delivered voltage pulses ranging from 900 to 1,700 volts, completing the session.

The technical choreography matters because electroporation is unforgiving of sloppy planning. The electric field must cover the entire tumor volume homogeneously; any region that falls between electrodes may receive sub-lethal exposure and survive as a seed of recurrence. This is why careful pre-treatment planning and meticulous electrode placement are considered the linchpins of the technique, particularly for large or irregularly shaped lesions like the one in this case. Encouragingly, the procedure itself was uneventful. No immediate or delayed complications occurred, post-procedure monitoring revealed nothing concerning, and the child was discharged in stable condition. The team notes that the approach is also repeatable, an important attribute for a disease where residual lesions sometimes require more than one local intervention.

The follow-up imaging tells the story in two snapshots. One month after the procedure, magnetic resonance imaging revealed a necrotic, liquefied area of 20 by 20 millimeters within the treated field—direct evidence that the electroporated cells had died on schedule, consistent with the six-to-eight-week window in which electrochemotherapy’s radiological effects typically become apparent. The child then completed her maintenance phase of treatment with cis-retinoic acid and dinutuximab beta without any complications. Twelve months after the procedure, computed tomography and MIBG imaging delivered the decisive verdict: the mass had shrunk to 9.2 by 8.9 by 9.4 centimeters, and, critically, no residual MIBG uptake could be detected anywhere in the treated area. The metabolically active component that had survived everything modern pediatric oncology could throw at it had been silenced.

Why does the disappearance of MIBG avidity matter so much? MIBG is a norepinephrine analog that is taken up specifically by neuroblastoma cells, so persistent tracer uptake is a molecular signature of living tumor. In neuroblastoma, residual primary disease that remains MIBG-avid after multimodal treatment is a well-established negative prognostic factor, strongly correlated with relapse and poor survival. The ability to selectively target and neutralize these metabolically active foci—without opening the abdomen, without thermal energy that could damage vessels and adjacent organs, and without adding systemic toxicity—addresses one of the most frustrating gaps in current therapy. Thermal ablation techniques such as radiofrequency ablation and cryoablation have been used in selected pediatric tumors, but they are hazardous near major vessels, which act as heat sinks and limit ablation margins, and near structures like the celiac artery that cannot tolerate thermal injury. Electrochemotherapy’s non-thermal mechanism sidesteps that constraint, and the authors note that its effects are applicable across tumor histologies, including tumors resistant to other modalities.

The caveats are as important as the promise. This is a single case, reported by the team of Giulia Cassanelli, Maria Antonietta De Ioris, and Gian Luigi Natali, and pediatric oncology is littered with promising one-patient results that failed to generalize. The authors themselves are careful, framing electrochemotherapy as a feasible local option for selected patients and calling for further evaluation within a multidisciplinary framework rather than declaring a new standard of care. Yet the signals here are hard to dismiss: a first-in-child application performed safely in one of the most anatomically hostile locations imaginable, durable local control of the exact tumor component that predicts relapse, and a treatment that can be repeated if needed. If larger studies confirm these findings, children with refractory neuroblastoma whose tumors are deemed inoperable may one day have an option that today they lack entirely—a minimally invasive, precisely targeted way to finish what chemotherapy, antibodies, and radiation started.

Subject of Research: Electrochemotherapy for residual MIBG-avid disease in refractory pediatric neuroblastoma

Article Title: Electrochemotherapy as a potential local treatment for residual MIBG-avid disease in refractory pediatric neuroblastoma: a case report

Article References: Cassanelli, G., De Ioris, M. A., & Natali, G. L. (2026). Electrochemotherapy as a potential local treatment for residual MIBG-avid disease in refractory pediatric neuroblastoma: a case report. CVIR Oncology, 2(1), Article 3. https://doi.org/10.1007/s44343-026-00032-8

Image Credits: AI Generated

DOI: 10.1007/s44343-026-00032-8

Keywords: neuroblastoma, electrochemotherapy, electroporation, cisplatin, pediatric oncology, interventional radiology, MIBG imaging, tumor ablation, MYCN amplification, residual disease, case report, local therapy

Plasmids are circular pieces of DNA that can be engineered to carry therapeutic genes into cells. Unlike viral vectors, which have dominated gene therapy because of their efficiency at transferring genetic material, plasmids are comparatively simple to manufacture, can carry larger payloads, and tend to raise fewer safety concerns related to insertional mutagenesis or uncontrolled viral replication. Their principal limitation has always been delivery: naked DNA does not readily cross cell membranes, and achieving clinically meaningful levels of gene expression inside tumors without a viral carrier has proven challenging. The new research addresses this obstacle by pairing an optimized plasmid combination with an intratumoral delivery approach, injecting the therapeutic construct directly into accessible lesions so that high local concentrations of the encoded proteins are produced precisely where they are needed most.

The therapeutic logic behind intratumoral plasmid delivery rests on a concept that has reshaped modern cancer immunotherapy: the idea that a tumor can be converted from a site of immune evasion into the equivalent of an in situ vaccine. When immune-stimulating genes are expressed inside a tumor, dying cancer cells release tumor antigens together with danger signals, and dendritic cells that traffic through the injected lesion can capture these antigens and carry them to draining lymph nodes. There, T cells are primed against the specific mutations and proteins of that patient’s cancer. Because melanoma is among the most mutationally dense of all human tumors, it presents a rich array of neoantigens, making it a particularly suitable candidate for this kind of localized priming strategy. Once activated, T cells can circulate through the bloodstream and attack metastatic deposits far removed from the injection site, a systemic effect commonly described as an abscopal response.

The combination described in the study was designed so that each plasmid component contributes a complementary function to this immunological cascade. One element is intended to drive the production of immune-activating cytokines within the tumor microenvironment, counteracting the immunosuppressive conditions that melanomas establish through regulatory T cells, suppressive macrophages, and inhibitory signaling pathways. Additional plasmids support antigen presentation and local inflammation, ensuring that the tumor becomes visible to the immune system rather than remaining immunologically silent. By encoding several factors simultaneously on separate but co-delivered plasmids, the approach avoids the cargo-size constraints that limit many viral vectors and allows the relative composition of the mixture to be tuned, something that fixed viral constructs cannot easily achieve.

Technically, the delivery of plasmid DNA into cells in vivo is typically enhanced by electroporation, a process in which short electrical pulses are applied to the injected tissue to transiently permeabilize cell membranes, allowing DNA to enter. Intratumoral electroporation has been explored in multiple clinical trials of cancer gene therapy, and its safety profile has been well characterized: the procedure is minimally invasive, can be performed under local anesthesia for accessible lesions, and confines gene expression largely to the treated tissue. This spatial restriction is an important safety feature, because it limits systemic exposure to cytokines that, when delivered as recombinant proteins throughout the body, can cause severe toxicity. The authors of the new work built on this established foundation, refining both the genetic composition of the plasmid cocktail and the parameters of its administration to maximize expression levels and antitumor activity.

The reported outcome, high levels of metastatic melanoma regression, is significant for several reasons. First, regression extended beyond the directly injected lesions, indicating that the treatment did more than destroy the cells physically contacted by the needle. This systemic component is the essential requirement for any therapy intended to control metastatic disease, in which tumor deposits are scattered across the skin, lymph nodes, lungs, liver, brain, and other organs. Second, the magnitude of the response suggests that the plasmid combination achieved biologically meaningful expression levels, overcoming the historical weakness of non-viral delivery. Third, the strategy is modular: because plasmids are cheap and quick to produce under good manufacturing practice conditions, alternative gene combinations could in principle be swapped in for different tumor types or to overcome resistance mechanisms as they emerge.

The implications for combination therapy are particularly noteworthy. Current standards of care for advanced melanoma include anti-PD-1 antibodies, sometimes combined with anti-CTLA-4 blockade, and BRAF plus MEK inhibitors for patients whose tumors carry BRAF V600 mutations. Each of these approaches eventually encounters resistance. An intratumoral plasmid therapy that generates local inflammation and broad neoantigen-specific T cell priming could act synergistically with checkpoint inhibitors, which function by releasing the brakes on T cells that have already been activated. In this sense, plasmid-based intratumoral treatment addresses the ignition problem, priming and expanding antitumor immunity, while checkpoint blockade addresses the brake problem, sustaining that immunity once it exists. Clinical trials testing such rational combinations are a natural next step for the field, and the preclinical findings reported here provide the mechanistic justification for pursuing them.

Safety and manufacturability considerations also weigh in favor of the plasmid approach. DNA plasmids are non-infectious, do not integrate efficiently into the genome, and can be produced at scale in bacterial fermentation at costs far below those of engineered viral vectors or personalized neoantigen vaccines. For patients, intratumoral administration means that only lesions reachable by injection can be treated directly, which is a limitation for visceral disease, although the demonstrated abscopal effect means that even a single injected lesion can, in principle, drive immunity against distant deposits. The procedure also allows repeated dosing, since DNA expression is transient by design, and transient expression of potent immunostimulatory molecules is generally safer than continuous systemic exposure.

The study adds momentum to a broader revival of interest in non-viral gene delivery, a field currently energized by the success of lipid nanoparticles in RNA therapeutics. Plasmid DNA and RNA-based approaches differ in important ways, with plasmids offering nuclear delivery and potentially longer expression, and the present work demonstrates that, with the right construct design and delivery conditions, non-viral DNA can reach the expression levels required for robust therapeutic activity in cancer. For metastatic melanoma patients whose disease has stopped responding to approved immunotherapies, and for the clinicians caring for them, the prospect of a simple, reproducible, and manufacturable intratumoral treatment that recruits the immune system against the full antigenic breadth of their own tumor represents a meaningful and cautiously encouraging advance. Continued preclinical validation and, ultimately, controlled clinical testing will determine how this novel plasmid combination fits into the evolving treatment landscape of advanced melanoma.

Subject of Research: Intratumoral plasmid gene delivery for the treatment of metastatic melanoma

Article Title: Intratumor delivery of a novel plasmid combination induces high levels of metastatic melanoma regression

Article References: Heller, L. C., Singh, J. S., Synowiec, J. C., Jaroszeski, M. J., Otten, A., & Heller, R. (2026). Intratumor delivery of a novel plasmid combination induces high levels of metastatic melanoma regression. Gene Therapy. https://doi.org/10.1038/s41434-026-00644-y

Image Credits: AI Generated

DOI: 10.1038/s41434-026-00644-y

Keywords: metastatic melanoma, plasmid DNA, intratumoral delivery, gene therapy, cancer immunotherapy, non-viral vectors, electroporation, antitumor immunity, abscopal effect, checkpoint inhibitors, tumor microenvironment, melanoma regression

TENGs were first reported in 2012 by Zhong Lin Wang and colleagues, and they work by exploiting a phenomenon most people regard as a nuisance: static electricity. When two materials with different electron affinities repeatedly contact and then separate, electrons transfer between them, leaving one surface positively charged and the other negatively charged. As the surfaces part, the accumulated charge creates a potential difference that drives electrons through an external circuit, producing usable electrical output. Wang later grounded the technology in theory by extending classical Maxwell’s equations through the concept of displacement current, showing that the time-dependent change in surface polarization acts as the primary driving force for induced current. Unlike conventional electromagnetic generators that rely on magnetic flux, TENGs generate current through dynamic electrostatic potential changes caused by periodic mechanical deformation, which makes them exceptionally good at harvesting low-frequency biomechanical energy such as walking, breathing, heartbeat or organ motion.

This output profile, high voltage combined with low current and pulsed waveforms, is precisely what makes TENGs attractive for oncology. Conventional electrical stimulation therapies require external power supplies, wired instrumentation and bulky equipment; electroporation systems use high-voltage pulses that risk collateral tissue damage; and tumor-treating fields, while clinically validated in selected malignancies, demand continuous device wear and carry high treatment costs. TENG systems, by contrast, are flexible, lightweight, biocompatible and entirely self-powered, drawing their energy from the body’s own movement. The devices operate in four fundamental modes: vertical contact-separation, single-electrode, linear sliding and freestanding triboelectric-layer configurations. Each mode shares the same underlying physics but differs in structure and motion pattern, giving engineers the flexibility to embed TENGs in wearables, implantables, smart textiles and self-powered environmental monitors.

One of the most striking applications described in the review is cancer prevention through environmental monitoring. Because most TENG platforms cannot yet detect tumor biomarkers directly, researchers have focused them on the carcinogenic exposures that precede malignancy. For respiratory cancer, the leading cause of cancer-related death worldwide, Wang and colleagues built a respiration-driven formaldehyde sensor using a titanium carbide MXene and ammonium-functionalized carbon nanotube triboelectric layer that detected the carcinogen at concentrations as low as 10 parts per billion, with response and recovery times of just 51 and 57 seconds. Yang and colleagues coupled a rotating TENG to a photocatalytic purification system, boosting formaldehyde degradation to 79.2 percent within 90 minutes, roughly 13 percent better than uncoupled systems. For benzene, Khandelwal and colleagues created a self-powered cellulose acetate and PVDF-titania sensor that achieved an 80 percent response at high concentrations and included a built-in alarm circuit requiring no external battery.

Particulate matter, another major lung cancer risk, has been tackled with triboelectric air filtration systems. Li and colleagues showed that a PTFE and polyester fiber-based filter raised short-term filtration efficiency from 36.7 percent to 74.6 percent and removed 99 percent of PM2.5 within 30 minutes, while Zheng and colleagues demonstrated a filter-free electrostatic purifier that used a TENG generating roughly 2 kilovolts to cut PM2.5 concentration in a test chamber from 954 to 50 micrograms per cubic meter in under 200 seconds, with minimal ozone production. For skin cancer, Zhang and colleagues developed a portable ultraviolet photodetector powered by a contact-separation TENG producing about 60 volts per cycle, and Cheng and colleagues wove TENG fibers into a multifunctional fabric offering an ultraviolet protection factor of 328, UV transmittance of only 0.21 percent, radiative cooling that kept the surface nearly 7 degrees Celsius cooler than cotton, and antibacterial inhibition rates above 98 percent against common pathogens.

The preventive reach of TENGs extends into the gastrointestinal tract, liver, colon and oral cavity. He and colleagues built an ethanol vapor sensor from a beta nickel hydroxide and MXene composite that detected exhaled ethanol below 200 parts per million with response and recovery times of 15 and 4 seconds even at 87 percent relative humidity, enabling battery-free screening for alcohol-related cancer risk. Cai and colleagues created a wood-based wireless gas sensor that detects ammonia released by spoiling food, a surrogate marker for aflatoxin, the well-known liver carcinogen, distinguishing clean air from 340 parts per million ammonia with recovery times under 11 seconds. Guo and colleagues went further, integrating a TENG producing roughly 380 volts with an electrowetting valve and a paper microfluidic device to automate enzyme-linked detection of alpha-fetoprotein, a hepatocellular carcinoma biomarker, completing the entire analysis in 260 seconds. Against Escherichia coli O157:H7, a microbe linked to colorectal cancer, Jin and colleagues’ rotating TENG powered ultraviolet lamps that reduced bacterial contamination on apple surfaces to 42 percent of original levels within an hour, while Luo and colleagues used a nine-thousand-volt TENG output to inactivate roughly 98 percent of E. coli and Staphylococcus aureus in water through electroporation.

On the therapeutic side, the review catalogues a series of remarkable preclinical results. Khayamian and colleagues developed a TENG-driven balloon catheter for irreversible electroporation of breast cancer tissue left behind after breast-conserving surgery; treated mice showed a 94 percent reduction in tumor volume within 15 days, whereas untreated controls saw tumors grow by 303 percent. Critically, irreversible electroporation induces immunogenic cell death, releasing tumor antigens and damage-associated molecular patterns that recruit dendritic cells and activate T cell responses, converting a local ablation into a systemic anticancer stimulus. Li and colleagues’ braided direct-current TENG, delivering 8,000 volts through stimulation needles inserted directly into tumors, shrank tumor mass by about 87 percent in mice within two weeks without damaging surrounding vessels. In the catalytic domain, Zhong and colleagues showed that TENG-generated electric fields modulate the d-band electrons of copper single-atom nanozymes, amplifying free radical production and oxidative tumor damage, while Yao and colleagues achieved an 83.6 percent tumor inhibition rate using electrical stimulation alone by boosting nanozyme catalytic activity fourfold and increasing current flow through conductive hydrogel injection.

Gas therapy and gene delivery round out the therapeutic arsenal. Yao and colleagues built a wearable stretchable TENG that wirelessly powers an implantable nitric oxide releasing device for glioma, increasing nitric oxide release by 183 percent compared with button cells and achieving at least 90.9 percent tumor inhibition over 14 days, with complete eradication in one case. Because nitric oxide above micromolar concentrations selectively kills cancer cells while sparing healthy tissue, and given its half-life of only a few minutes, such precision self-powered delivery is a significant advance. In gene therapy, Yang and colleagues demonstrated a TENG-driven nanowire electrode array that delivered siRNA to pancreatic cancer and leukemia cells in just 40 seconds, suppressing oncogene expression including KRAS and BCR-ABL while maintaining roughly 90 percent cell viability, with delivery efficiencies exceeding 95 percent in cells that are notoriously difficult to transfect. The team also paired an implantable magnetic TENG with doxorubicin-loaded red blood cells, using electroporation to trigger drug release at very low concentrations, and described ultrasound-activated Trojan nanogenerators combining electrical stimulation with catalytic therapy.

Perhaps most provocative is the emergence of triboelectric immunotherapy. Li and colleagues showed that a small fabric direct-current TENG, just 6.8 by 7 centimeters, could generate sufficient pulsed direct current to induce immunogenic cell death in tumor cells, driving dendritic cell maturation, T cell differentiation and durable antitumor immunity without any drug at all. The same group later combined this drug-free approach with CD19-targeted CAR-T cells against solid tumors, promoting M1 macrophage polarization, reducing regulatory T cells and enhancing CAR-T infiltration to eradicate nearly 60 percent of tumor mass, with the CAR-T cells differentiating into memory T cells that provided long-term protection against recurrence. The authors caution that substantial obstacles remain before clinical translation: long-term biocompatibility and degradation studies are needed, electrophysiological risks such as unintended cardiac or nerve stimulation must be rigorously controlled, and output variability across devices and patients demands standardized fabrication, calibration and dosing protocols. Still, if those challenges can be met, TENG technology could bridge environmental sensing, behavioral modification and preventive oncology into a single sustainable framework, transforming biomechanical energy itself into a tool against cancer.

Subject of Research: Triboelectric nanogenerators for cancer prevention, therapy and immunotherapy

Article Title: Triboelectric nanogenerators for cancer prevention and therapy: a new paradigm in cancer management

Article References: Dandugudumula, R., & Shin, D. Y. (2026). Triboelectric nanogenerators for cancer prevention and therapy: a new paradigm in cancer management. Advances in Industrial and Engineering Chemistry, 2(1), Article 8. https://doi.org/10.1007/s44405-026-00048-x

Image Credits: AI Generated

DOI: 10.1007/s44405-026-00048-x

Keywords: triboelectric nanogenerators, cancer therapy, energy harvesting, immunotherapy, drug delivery, electroporation, carcinogen monitoring, nanozymes, CAR-T cells, wearable sensors, implantable devices, nitric oxide therapy