At the heart of Zhang’s research lies a deceptively simple idea: rather than trying to engineer, molecule by molecule, a synthetic particle capable of navigating the treacherous terrain of the human bloodstream, why not simply borrow the camouflage that nature has already perfected? His laboratory takes membranes harvested from human cells and wraps them around biodegradable nanoparticles roughly one-thousandth the width of a human hair. Once cloaked, these particles inherit some of the biological powers of the cells they mimic. Red blood cell membranes allow the particles to circulate undetected for extended periods, delivering drugs to the tissues that need them. White blood cell membranes endow the particles with an entirely different talent: the ability to soak up and neutralize the toxic molecules that drive sepsis, to attack infection-causing fungi, and even to intercept the inflammatory signals that fuel rheumatoid arthritis.

The insight emerged from a longstanding frustration in nanomedicine. Nanoparticles can carry enormous payloads of medicine relative to their size, but once injected into the bloodstream they run headlong into the immune system, a surveillance network exquisitely designed to eliminate anything that does not belong. Researchers had long tried to make synthetic particles less conspicuous, coating them with polymers and other materials intended to suppress immune recognition, with limited success. Zhang’s alternative was more radical and, in retrospect, more elegant. Instead of making synthetic particles harder to recognize, he would make them genuinely recognizable as self. His team began with red blood cells, collecting their membranes and wrapping them around nanoparticles while carefully preserving the proteins, lipids, and carbohydrates that naturally stud the cell surface.

The landmark demonstration came in 2011, when Zhang’s group published a paper in the Proceedings of the National Academy of Sciences showing that membrane-coated nanoparticles could circulate in the bloodstream for up to two days, far longer than many conventional nanoparticles of the era. Zhang has often described the strategy as an engineering shortcut. Recreating the staggering molecular complexity of a cell surface from scratch, with its precisely organized arrays of proteins, lipids, and carbohydrates, would be a monumental synthetic challenge. Using the membrane itself sidesteps that problem entirely. The beauty of the technology, as Zhang puts it, is that the complexity does not have to be rebuilt; it can simply be transferred intact onto the surface of a particle small enough to travel wherever the blood goes.

The disguise offered far more than extended circulation time. Red blood cells are natural targets for bacterial toxins that kill cells by punching holes in their membranes, and particles dressed as red blood cells proved irresistible to those toxins. Zhang’s team christened these decoys nanosponges for their ability to soak up toxins and divert them away from real cells. The approach showed promise against toxins produced by dangerous bacteria, including methicillin-resistant Staphylococcus aureus, better known as MRSA. By removing toxins from circulation, the nanosponges helped weaken MRSA infections, and because the strategy does not depend on antibiotics at all, it points toward a way of treating drug-resistant infections without fueling the resistance crisis that has rendered so many conventional drugs ineffective.

From that first success, Zhang began borrowing membranes from an expanding cast of cell types. His laboratory developed macrophage-coated nanosponges to capture the toxins and inflammatory molecules involved in sepsis, the uncontrolled immune response triggered by bacterial infection that can cascade into organ damage and death. Because macrophage membranes carry receptors for a broad spectrum of sepsis-causing molecules, the particles function as universal traps rather than single-target drugs, an approach Zhang argues is more effective than attacking one disease-causing molecule at a time. Neutrophil-coated nanosponges followed, designed to treat rheumatoid arthritis. Neutrophils are immune cells that rush to sites of inflammation, where they can perpetuate a chain reaction of tissue damage; the neutrophil nanosponges acted as decoys, intercepting inflammation-causing molecules before they could keep the destructive cycle turning.

More recently, the concept has been extended to drug-resistant fungal infections caused by Candida albicans, the organism behind common yeast infections and, in severe cases, deadly bloodstream infections. Since macrophages naturally recognize Candida, Zhang’s researchers used macrophage membranes to build nanoparticles that could seek out fungal cells. In experiments, the particles attached to Candida cells, physically damaged them, and helped stimulate the body’s own immune defenses. The same membrane-borrowing principle has also produced platelet-coated nanoparticles for targeted drug delivery. Platelets, the tiny cell fragments that bind to damaged blood vessels to stop bleeding, also preferentially bind to certain pathogens, including MRSA. When loaded with medicine, the platelet-disguised particles delivered their cargo directly to damaged arteries and bacterial infections, healing them with only a fraction of the typical dose while minimizing side effects elsewhere in the body.

For Zhang, the urgency of translating laboratory discoveries into real medicine has a deeply personal origin. When he joined UC San Diego in 2008, his laboratory was housed in the Moores Cancer Center, where he watched dozens of cancer patients pass through the building every day. That environment, he has said, provided a natural intersection between engineering and medicine, and seeing so many people suffering left him feeling a scientist’s responsibility to do something that could make a difference. His path to that mission was unconventional. As an undergraduate studying chemical engineering at Tsinghua University in Beijing, he helped develop an unusually tough plastic and could have commercialized it and opened a factory. Instead he left for a Ph.D. in chemical engineering at the University of Illinois at Urbana-Champaign and a postdoctoral fellowship at MIT. Though the plastics factory never materialized, his entrepreneurial instincts did: he co-founded biotech startups, including San Diego-based Cellics Therapeutics, which is working to move the red blood cell and macrophage nanosponges toward clinical studies for bacterial infections, autoimmune diseases, and inflammatory diseases, while also exploring cellular nanoparticles that could neutralize a wide variety of pathogens, including bacterial toxins and viruses.

That commitment to scalability now shapes his leadership as chair of his department, where he has worked to bridge the traditionally separate territories of chemical engineering and nano engineering. Nano engineering, as Zhang explains it, centers on innovative nanoscience and technologies operating at very small scales, while chemical engineering focuses on large-scale production, manufacturing, and the processes that turn materials into products. His effort to fuse the two was recognized with a $21 million gift to the department in 2024 from San Diego business leader and philanthropist Aiiso Yufeng Li and his family, and the merged department now operates under the slogan Scalable Innovation, allowing undergraduates to move seamlessly between nanoscale science and the realities of manufacturing at scale. Zhang’s career has accumulated a long list of distinctions along the way: election as a fellow of the National Academy of Inventors in 2020, the American Association for the Advancement of Science in 2018, and the American Institute for Medical and Biological Engineering in 2015, plus recognition on Popular Science’s Brilliant 10 list in 2016, MIT Technology Review’s top 35 young innovators in 2013, and repeated appearances among Clarivate’s Most Highly Cited Researchers.

The reach of Zhang’s idea now extends well beyond his own laboratory. In the past decade, more than 10,000 papers on cell membrane coating technology have been published by hundreds of laboratories worldwide, a testament to how thoroughly the approach has permeated the field. Zhang notes that laboratories around the globe are using the technology to advance their own research, an impact that reaches researchers he may never meet. At UC San Diego, he joins a select company of MacArthur Fellows on the current faculty, including computer science and engineering professor Stefan Savage, Division of Social Sciences Dean Carol Padden, anthropology professor Guillermo Algaze, and philosophy professor Nancy Cartwright, along with several emeritus recipients. Chancellor Pradeep K. Khosla congratulated Zhang on what he called a tremendous, well-deserved honor, crediting the professor with turning cellular membranes into a platform technology to deliver medicines and combat infectious disease and inflammation. As the fellowship’s unrestricted funds free him to pursue whatever directions he chooses, the cellular disguises that began as an engineering shortcut now stand as one of the most influential ideas in modern nanomedicine, with the potential to redefine treatment for cancer, infection, and inflammatory disease alike.

Subject of Research: Cell-mimicking nanoparticles for drug delivery and treatment of infectious and inflammatory diseases

Article Title: Nanomedicine pioneer at UC San Diego awarded MacArthur ‘Genius Grant’

Article References: Nanomedicine pioneer at UC San Diego awarded MacArthur ‘Genius Grant’. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: MacArthur Fellowship, nanomedicine, cell membrane-coated nanoparticles, drug delivery, nanosponges, antibiotic resistance, sepsis, rheumatoid arthritis, MRSA, Candida albicans, UC San Diego, biotechnology

For decades, biomaterials in medicine were conceived as inert scaffolds or passive delivery vehicles, designed to ferry drugs to their targets while provoking as little immune reaction as possible. That paradigm has inverted. The review highlights how materials spanning inorganic nanoparticles, synthetic polymers, natural biomacromolecules, and cell-derived vesicles are now deliberately designed to engage and reprogram macrophages, dendritic cells, T lymphocytes, and innate lymphoid cells. Because these materials can act as immune activators or suppressors depending on their chemistry, size, shape, and context, they offer a versatile platform for treating inflammation, cancer, infection, and autoimmune disease. The authors emphasize that targeted drug delivery and immuno-engineering are only part of the story; the intrinsic immunomodulatory properties of the materials themselves must not be overlooked.

Inorganic nanomaterials occupy a prominent place in this landscape because of their superior physicochemical stability and controllability. Their non-self nature means the immune system recognizes them as foreign, activating phagocytic cells such as macrophages and dendritic cells. While this inflammatory response would be undesirable in healthy tissue, it can paradoxically enhance tumor immunotherapy. Gold nanorods, fullerene derivatives, and graphene oxide derivatives have all demonstrated capacity as vaccine adjuvants, inducing localized inflammation that strengthens immune protection against viral infections and malignancies. A particularly intriguing subset, known as nanozymes, exhibits intrinsic enzyme-like catalytic activity whose output depends on particle size, structure, cellular internalization, and environmental pH, allowing them to either raise or lower reactive oxygen species concentrations in chronic inflammatory microenvironments.

Iron oxide nanoparticles illustrate the clinical maturity of this approach. Several formulations have already been approved by the U.S. Food and Drug Administration as magnetic resonance imaging contrast agents, treatments for iron deficiency, and components of nano-vaccine platforms. Beyond these established uses, studies show that iron oxide nanoparticles can drive M1 polarization of macrophages, boosting production of reactive oxygen species, tumor necrosis factor-alpha, and nitric oxide to inhibit tumor progression. In one reported mechanism, uptake of these particles by macrophages raises intracellular iron and activates the NF-κB signaling pathway, triggering TNF-α-mediated immune activation. The particles also display enzyme-like behavior: ultrasmall Fe₃O₄ nanoparticles act as peroxidases under acidic conditions, decomposing hydrogen peroxide into hydroxyl radicals that kill cancer cells, while a catalase-mimicking material called fenozyme has reduced mortality in experimental cerebral malaria by lowering reactive oxygen levels and promoting macrophage polarization.

Manganese-based nanomaterials have emerged as equally potent immunological tools. Manganese ions markedly enhance the sensitivity of the cGAS–STING pathway, a central innate immune sensor that recognizes microbial and endogenous DNA. Research cited in the review shows that Mn²⁺ increases antigen presentation by dendritic cells and macrophages, facilitating activation of natural killer cells and T lymphocytes, and that combining this effect with anti-PD-1 checkpoint blockade yields notable therapeutic efficacy. Researchers have also developed coordination nanoparticles that self-assemble from manganese ions and a STING agonist, producing enhanced interferon responses and robust antitumor immunity in treatment-resistant tumor models, and manganese-based nano-vaccines have shown promise in preclinical models of SARS-CoV-2 infection. Other metal systems extend the catalog: nanoscale titanium dioxide with nanospike structures exerts mechanical stress on phagocytosing immune cells, triggering potassium efflux and inflammasome activation, while ultrasmall copper oxide nanozymes scavenge reactive oxygen species and ameliorate acute liver injury, diabetic wounds, and acute kidney injury.

Silicon nanoparticles tell a story of transformation from hazard to therapeutic. Unmodified silica can provoke inflammatory responses through interactions with monocytes and the complement system, and accumulation of silica dioxide particles in lung tissue has been shown to create a premetastatic niche in healthy mice. Yet in tumor-bearing organisms this immunostimulatory character becomes an asset. Ultrasmall silica nanoparticles can initiate T cell activation through direct particle–cell interactions in a dose-dependent manner, and certain formulations have progressed to human clinical trials. Hollow mesoporous silica nanoparticles function as immunoadjuvants that enhance both Th1 and Th2 responses, elevate effector memory T cell populations in the bone marrow, and, remarkably, when administered intraperitoneally, significantly improve the response to PD-1 checkpoint blockade by targeting tumor-associated macrophages, activating the Toll-like receptor 4–NF-κB cascade, and increasing secretion of T cell–recruiting chemokines. For immunologically cold tumors, this strategy of amplifying local inflammation is compelling.

Carbon-based nanomaterials present a more complicated picture. Graphene oxide acts as a natural antioxidant, reducing reactive oxygen species in macrophages and mitigating M1 polarization, and graphene quantum dots have suppressed Th1/Th17 polarization, promoted regulatory T cell ratios, and alleviated intestinal inflammation in murine models of enteritis. These quantum dots can even cross the blood–brain barrier and inhibit aggregation of alpha-synuclein fibrils, suggesting neuroprotective potential in Parkinson’s disease. However, concerns about carcinogenicity, particularly for carbon nanotubes, temper enthusiasm; prolonged exposure to multiwalled carbon nanotubes has been reported to intensify the invasiveness of implanted breast cancer cells and promote lung colonization. This duality, in which the same inflammatory capacity that makes a material a useful adjuvant can also pose long-term risks, remains one of the field’s central unresolved problems.

Organic and cell-derived biomaterials offer biocompatibility advantages that inorganic systems struggle to match. Synthetic polymer hydrogels have been engineered to initiate type-2 adaptive immune responses that promote skin regeneration, and acid-responsive polymeric nanoparticles that target lymph nodes and activate the STING pathway have spawned optimized, degradable successors. Cationic nanoparticles composed of PLGA–PDMA block copolymers can scavenge cell-free DNA, reducing inflammatory activation in rheumatoid arthritis models. Natural biomacromolecules carry inherent activity: fungal polysaccharides, yeast cell wall beta-glucans, and hyaluronic acid all modulate macrophage polarization and T cell responses, with hyaluronic acid’s effects shifting depending on molecular weight. DNA nanostructures built through programmable base pairing can deliver CpG oligonucleotides, potent Toll-like receptor 9 agonists, into immune cells with high specificity, and a rectangular DNA origami nanorobot decorated with immune agonists has trafficked to draining lymph nodes and evoked durable tumor-specific immune responses. Perhaps most striking are cell membrane-coated nanoparticles: mesenchymal stem cell membranes displaying PD-L1 have suppressed excessive T cell activation and eased immune-related adverse events from checkpoint blockade, macrophage membrane nanosponges have sequestered inflammatory cytokines in atherosclerosis and sepsis models, and fusion nanodecoys combining ACE2-expressing membranes with monocyte membranes have simultaneously neutralized virus and absorbed cytokines in COVID-19 research. Exosomes, the nanoscale vesicles cells use to communicate, add another layer, with phenotype-dependent functions ranging from tumor repolarization to insulin sensitization.

The review’s authors are candid about the obstacles standing between laboratory promise and clinical routine. Incomplete degradation, unintended biodistribution, and persistent low-grade inflammation may lead to fibrosis, granuloma formation, or off-target immunotoxicity, demanding long-term in vivo studies and standardized evaluation protocols. Inorganic materials raise questions about ion release and oxidative stress during degradation, while polymers suffer from batch-to-batch variability and complex manufacturing that hinders scalability. Exosome production remains inefficient and heterogeneous, and endotoxin contamination, even at trace levels, can confound experimental results entirely. Looking forward, the authors point to single-cell sequencing, spatial transcriptomics, and artificial intelligence-driven material screening as technologies that could illuminate how biomaterials shape immune microenvironments and accelerate rational design. They also envision personalized immunomodulatory biomaterials tailored to individual immune profiles, and feedback-responsive systems capable of achieving controlled, localized, transient immune activation without systemic toxicity. If those challenges can be met, the materials described in this synthesis may do more than carry the next generation of immunotherapies; they may become the therapies themselves, precisely engineered to teach the immune system when to fight and when to stand down.

Subject of Research: Immunomodulatory biomaterials for immunotherapy

Article Title: Advances and projects of immunomodulatory biomaterials used for immunotherapy

Article References: Frumento, D., & Patra, N. (2026). Advances and projects of immunomodulatory biomaterials used for immunotherapy. Holistic Integrative Oncology, 5(1), Article 78. https://doi.org/10.1007/s44178-026-00296-3

Image Credits: AI Generated

DOI: 10.1007/s44178-026-00296-3

Keywords: immunomodulatory biomaterials, immunotherapy, nanozymes, iron oxide nanoparticles, manganese adjuvants, STING pathway, mesoporous silica nanoparticles, graphene quantum dots, cell membrane-coated nanoparticles, exosomes, macrophage polarization, cancer immunotherapy

Graphitic carbon nitride, often abbreviated as g-C3N4, is a two-dimensional polymeric material composed of carbon and nitrogen arranged in heptazine or triazine ring structures. It has attracted intense interest in photocatalysis because it absorbs visible light, is chemically robust, and contains no heavy metals. In biomedical contexts, these properties matter enormously: nanoparticles that persist in the body must not leach toxic ions, and materials activated by light in the visible or near-infrared range can be triggered from outside the body with spatial precision. What has limited clinical translation, however, is that bare carbon nitride particles are recognized and cleared by the immune system, aggregate in physiological salt concentrations, and lack any built-in affinity for the diseased tissues they are meant to treat.

The new study addresses these shortcomings by wrapping the nanoparticles in natural cell membranes, a strategy known as biomimetic coating. By cloaking graphitic carbon nitride nanoparticles in membranes derived from cells, the researchers effectively gave the particles a biological disguise. The membrane coating preserves the surface markers and proteins that cells use to communicate with their surroundings, allowing the nanoparticles to evade rapid immune clearance, navigate the complex protein milieu of blood, and preferentially accumulate at target sites such as tumors or inflamed tissue. This approach borrows directly from the way pathogens and circulating tumor cells disguise themselves to survive in the bloodstream, turning a survival trick of biology into an engineering tool.

The phrase multiscale photomodulation in the study’s title captures the platform’s defining feature. At the molecular scale, photoexcitation of graphitic carbon nitride generates electron-hole pairs that can drive the production of reactive oxygen species, the chemical basis of photodynamic therapy. At the cellular scale, these reactive species can damage cancer cell membranes, mitochondria, and DNA, triggering cell death pathways. At the tissue and organ scales, the particles’ light absorption and conversion properties can be harnessed for imaging, for localized heating through photothermal effects, and for modulating biological processes such as inflammation or neuronal activity. A single nanomaterial, the authors argue, can therefore serve as an optical actuator operating simultaneously at the molecular, cellular, and organismal levels.

Photodynamic therapy, one of the central applications, relies on photosensitizers that, upon light activation, transfer energy to ground-state oxygen to produce singlet oxygen and other cytotoxic reactive species. Conventional photosensitizers frequently suffer from poor water solubility, insufficient tissue penetration of the activating light, and off-target toxicity when illuminated light reaches healthy tissue. Graphitic carbon nitride nanoparticles offer an alternative photosensitizer with strong photocatalytic activity under visible light, high photostability that resists photobleaching, and a metal-free composition that simplifies regulatory and toxicity considerations. The biomimetic coating adds a layer of targeting that improves the therapeutic window by concentrating the photosensitizer where it is needed.

The therapeutic breadth described in the work extends beyond tumor ablation. Because light can be applied, removed, or tuned in real time, the platform functions as a programmable intervention: clinicians could in principle control the dose of reactive oxygen species or heat delivered to a lesion by adjusting illumination intensity, wavelength, and duration. The researchers describe applications in antimicrobial treatment, where photoinduced reactive species can kill drug-resistant bacteria without contributing to antibiotic resistance, and in immune modulation, where controlled photochemistry at the surface of membrane-coated particles can influence inflammatory signaling. Such versatility is rare in a single nanoplatform and reflects the underlying tunability of the semiconductor’s electronic structure.

A key technical achievement highlighted in the study is the stability of the membrane-nanoparticle hybrid in physiological conditions. Bare nanoscale semiconductors tend to aggregate in serum because proteins and salts screen electrostatic repulsion between particles. The biomimetic coating, by presenting a hydrated, biologically familiar surface, suppresses aggregation and prolongs circulation time. The coating also changes biodistribution: instead of being trapped rapidly by the liver and spleen, the disguised particles can circulate longer and exploit biological homing mechanisms, such as the affinity of tumor-cell membranes for their parent tumor tissue, to reach disease sites more efficiently. This homologous targeting principle has emerged in recent years as one of the most promising strategies in nanomedicine.

The work also speaks to a broader shift in how researchers think about the interface between synthetic materials and living systems. Rather than attempting to out-engineer biology with ever more exotic synthetic chemistries, the biomimetic approach integrates biological components directly into the material’s architecture. In this case, the rigid, optically active semiconductor core supplies the physical function, light harvesting and energy conversion, while the soft biological shell supplies the systemic function, immune evasion and targeting. The division of labor between core and shell illustrates a design philosophy that could extend to other two-dimensional materials, including transition-metal dichalcogenides and black phosphorus, which face similar barriers to biomedical use.

Safety remains a central question for any nanomaterial intended for clinical use, and the metal-free nature of graphitic carbon nitride is a meaningful advantage. Materials such as quantum dots containing cadmium or lead raise persistent concerns about long-term accumulation and ion release, whereas carbon nitride degrades into comparatively benign carbon- and nitrogen-containing species. The authors emphasize that biodegradability and clearance must still be rigorously characterized in advanced animal models and, eventually, in clinical trials, but the composition of the material removes an entire class of toxicity concerns at the outset.

The study’s authors position the platform as a foundation rather than a finished product. Future work, they suggest, could pair the particles with complementary light sources such as implantable LEDs or upconversion systems that shift near-infrared light into wavelengths the material absorbs more efficiently, extending treatment depth beyond the millimeter scale of conventional photodynamic therapy. Combining the photomodulation platform with immunotherapy, gene delivery, or responsive drug release could yield closed-loop systems in which light both diagnoses and treats. As biomimetic nanomaterials continue to mature, graphitic carbon nitride nanoparticles that speak the language of biology while harnessing the power of light may prove to be one of the more durable bridges between materials science and medicine.

Subject of Research: Biomimetic graphitic carbon nitride nanoparticles for multiscale photomodulation and light-activated therapeutic intervention

Article Title: Biomimetic graphitic carbon nitride nanoparticles for multiscale photomodulation and therapeutic intervention

Article References: Müller, C. A., Klompmaker, K. K., Zhang, Y., Zhang, J., Kalatanova, A., Li, P., Meng, L., Madsen, J. G., Jakobsen, T. S., Jørgensen, A. C., Askou, A. L., Luo, Y., Lin, L., Vogt Bleshøy, S., Bolis, G., Huang, G., Li, W., Davidsen, R. S., Bek, T., … Chen, M. (2026). Biomimetic graphitic carbon nitride nanoparticles for multiscale photomodulation and therapeutic intervention. Nature Biomedical Engineering. https://doi.org/10.1038/s41551-026-01773-w

Image Credits: AI Generated

DOI: 10.1038/s41551-026-01773-w

Keywords: graphitic carbon nitride, nanoparticles, biomimetic coating, photodynamic therapy, photomodulation, nanomedicine, reactive oxygen species, drug delivery, photothermal therapy, cell membrane coating, biodegradable nanomaterials, light-activated therapy

The foundations of this transformation are already established in the clinic. Liposomal doxorubicin and albumin-bound paclitaxel became FDA-approved cancer therapeutics decades ago, improving tolerability and therapeutic index for patients. The decisive proof of concept, however, came with the lipid nanoparticle platforms that enabled the rapid development and global deployment of mRNA vaccines against SARS-CoV-2. According to the authors, these milestones demonstrate not only that nanomedicine works, but that nanoscale engineering can accelerate the translation of advanced therapeutics, reshape response profiles, reduce toxicity and make molecular modalities previously infeasible in vivo a practical reality.

One of the most striking frontiers described in the perspective is the use of living cells as delivery vehicles. Rather than fighting the body’s biological barriers with synthetic materials alone, researchers are now exploiting them. Nanoparticles can hitchhike on red blood cells, dramatically reducing clearance by the liver and spleen while extending circulation time, and in some designs depositing their cargo preferentially in the lungs through contact-mediated dislodging from the cell surface. Discoidal polymer particles known as cellular backpacks ride on macrophages, monocytes, T cells, neutrophils and B cells, modulating immune cell behavior in applications ranging from cancer to multiple sclerosis and traumatic brain injury. These hybrid systems combine the precision of engineered materials with the navigation skills of the body’s own cells.

Immunology is emerging as a central arena for this new generation of nanotechnologies. Cell membrane–coated nanoparticles, or CNPs, wrap synthetic cores in natural cellular membranes, presenting native antigen repertoires that conventional vaccines struggle to replicate. Cancer cell membrane–coated particles elicit potent antitumor immunity, while bacterial outer membrane vesicle platforms preserve pathogen-associated molecular patterns to generate broad-spectrum protection, including against antimicrobial-resistant strains. Nanotoxoids take this further, detaining bacterial toxins on nanoparticle surfaces so the immune system can safely learn their shapes. Advances in membrane genetic engineering and modular linker chemistry are now turning these platforms into rapidly customizable, scalable vaccine systems.

Perhaps the most futuristic concept described is the living pharmacy: implanted, encapsulated cells that continuously manufacture biologics inside the body. The recent FDA approval of Neurotech’s ENCELTO, an encapsulated allogeneic cell therapy implanted in the eye, anchors the feasibility of the approach. Modern platforms combine synthetic biology programs that control what cells produce, biomaterials that tame the foreign body response while allowing oxygen and nutrient exchange, and device interfaces offering retrievability and external control, including electro- and optogenetic actuation. Key challenges ahead include improving volumetric efficiency, ensuring predictable dosing behavior and demonstrating durable performance in large-animal models.

On the cancer front, the perspective highlights how macrophages, long viewed as obstacles that clear nanoparticles from circulation, are being reprogrammed into therapeutic partners. Ultrasound-guided platforms deliver STING agonists directly to antigen-presenting cells, while constructs that disrupt the CD47 ‘don’t eat me’ signal enable macrophage-mediated tumor cell phagocytosis. Blocking the MARCO receptor reduces hepatic sequestration of nanoparticles, boosting tumor accumulation. In hypovascularized breast cancer liver metastases, redirecting albumin-bound paclitaxel transport toward macrophages significantly improves therapeutic outcomes in a setting where conventional intravenous delivery largely fails. Implantable nanofluidic drug-eluting seeds add another layer of control, sustaining localized intratumoral immunotherapy for more than four weeks and converting immunologically cold tumors into hot ones at a fraction of the systemic dose.

Polymer chemistry is advancing carrier performance in parallel. Poly(2-oxazoline) and poly(2-oxazine) micelles achieve drug loads ten to one hundred times higher than traditional micelles, enabling intravenous formulations with minimal excipient content. The first POx-based medical product, a hemostatic sealing patch, received European approval in 2023, and the absence of preexisting anti-POx antibodies makes these polymers attractive alternatives to polyethylene glycol, which is increasingly associated with immunogenicity. Vascular-confined discoidal nanoconstructs carrying tissue plasminogen activator, meanwhile, recanalize roughly ninety percent of occluded venules in mouse models compared with about forty percent for free tPA, while preserving neurological outcomes and improving survival in stroke models.

Gene and RNA nanotherapies represent another pillar of the expanded field. In vivo CRISPR delivery via lipid nanoparticles aims to democratize access to genetic cures, bypassing the roughly 2.2 million dollar per patient cost of autologous ex vivo editing. Mesoscale nanoparticles of 300 to 500 nanometers selectively target the renal proximal tubule, delivering siRNAs and mRNAs for kidney diseases that have historically been inaccessible to systemic RNA therapeutics. In the liver, a strategy termed Repair Drive uses transient siRNA inhibition of an essential gene to eliminate unedited hepatocytes, expanding precisely corrected cells from less than one percent to approximately twenty-five percent of the liver. Transient telomerase mRNA delivered by lipid nanoparticles is showing promise for protecting skin from radiation-induced DNA damage, operating through genome and mitochondrial maintenance rather than telomere extension.

The perspective also documents a radical extension of the concept: therapeutics built from organelles and biological vesicles themselves. Extracellular vesicles from brain endothelial cells carry functional mitochondria and, when administered intravenously after stroke in mice, significantly reduce brain infarct volume and improve neurological function. Exogenous mitochondrial transfer into plaque macrophages reduces atherosclerotic burden and improves markers of fatty liver disease, positioning mitochondrial transplantation as an emerging metabolic nanotherapy. Hybrid vesicles that merge extracellular vesicle targeting with synthetic liposome stability offer enhanced tumor accumulation with improved scalability over native EV preparations.

The authors close with a vision of a modular nanomedicine ecosystem in which nanoparticles behave like cells, cells function as therapeutic devices, devices operate as immunomodulators, and imaging technologies evolve into pharmacologic tools. Realizing that vision, they emphasize, will require manufacturing and quality-by-design frameworks that embed reproducibility, safety and scalability from the outset, translating laboratory ingenuity into clinical-grade platforms capable of sensing, computing and responding to disease in real time.

Subject of Research: The expansion of nanomedicine beyond drug carriers into implantable devices, cell-based systems and living therapeutics

Article Title: Nanomedicine beyond carriers — devices, cells & living therapeutics

Article References: Grattoni, A., Paci, M. M., Arnold, N., Aryal, S., Artzi, N., Bao, G., Barcena, A. J. R., Bentov-Arava, E., Blanco, E., Chua, C. Y. X., Corradetti, B., Cryer, A. M., Decuzzi, P., De Giorgi, M., Fell, C., Gao, W., Govindaswamy, B., Jiang, W., Kara, G., … Godin, B. (2026). Nanomedicine beyond carriers — devices, cells & living therapeutics. Biomedical Microdevices, 28(3), Article 65. https://doi.org/10.1007/s10544-026-00836-8

Image Credits: AI Generated

DOI: 10.1007/s10544-026-00836-8

Keywords: nanomedicine, drug delivery, lipid nanoparticles, mRNA vaccines, cell membrane-coated nanoparticles, immunotherapy, living pharmacies, CRISPR, extracellular vesicles, mitochondrial transfer, nanofluidic implants, poly(2-oxazoline)