The centerpiece of the strategy is lactate, a molecule that sits at the heart of tumor metabolism. Cancer cells favor glycolysis even in the presence of oxygen, a phenomenon known as the Warburg effect, and the resulting lactate accumulation acidifies the tumor microenvironment, fuels new blood vessel growth through HIF-1α/VEGF signaling, recruits immunosuppressive cells, and even modifies key proteins such as p53 and MRE11 through a recently discovered epigenetic process called lactylation. By targeting lactate directly, the researchers sought to undermine the tumor’s energy supply and reverse the microenvironmental features that promote resistance and malignant progression.

The vehicle for this attack is a hollow mesoporous manganese dioxide nanoparticle, or HMnO₂, whose high surface area and large pore volume allow it to carry both an enzyme and a light-sensitive drug. The enzyme, lactate oxidase or LOX, converts lactate into pyruvate and hydrogen peroxide; the manganese dioxide carrier then decomposes that hydrogen peroxide into oxygen, which in turn sustains further lactate oxidation. This closed loop, the researchers explain, is self-sustaining: the enzyme consumes lactate and oxygen, generates hydrogen peroxide, and the carrier recycles that peroxide back into the oxygen the enzyme needs. The cycle continuously drains the tumor’s metabolic fuel, simultaneously raising oxygen levels, lowering local pH, and starving cancer cells.

The catalytic cycle was verified in a series of in vitro experiments. In the presence of lactate, LOX alone generated 50.58 µM of hydrogen peroxide, but the full HILA nanoparticle produced 4.25 times more, demonstrating that the manganese carrier amplifies the enzymatic reaction by regenerating oxygen in situ. Whereas free LOX rapidly exhausted dissolved oxygen in solution, HILA’s oxygen consumption declined only gradually, confirming that the carrier compensates for the enzyme’s oxygen appetite. The nanoparticles also proved to be responsive triggers: they degraded more readily in acidic, glutathione-rich conditions characteristic of tumors, releasing their indocyanine green payload in a pH-, glutathione-, peroxide-, and heat-dependent fashion, with near-infrared irradiation further accelerating drug liberation.

That payload, indocyanine green, is an FDA-approved near-infrared dye already used for fluorescence navigation in colorectal surgery. It can simultaneously mediate photodynamic therapy by generating singlet oxygen and photothermal therapy by converting light into heat. Yet its clinical promise has been hampered by poor stability, weak tumor targeting, and the hypoxic nature of tumors, which starves photodynamic therapy of the oxygen it needs. HILA addresses all three limitations at once. The oxygen regenerated by the catalytic cycle keeps singlet oxygen production running, the photothermal effect speeds catalytic kinetics, and the released manganese ions perform a Fenton-like reaction that churns out lethal hydroxyl radicals for chemodynamic therapy.

The photothermal measurements were striking. Under 780-nanometer irradiation, HILA achieved a temperature rise of 22.80 °C, exceeding free indocyanine green, and its photothermal conversion efficiency reached 33.83 percent—competitive with black phosphorus and gold-based agents while offering the clinical advantage of biodegradable, clinically vetted components. In lactate-enriched conditions mimicking the tumor microenvironment, HILA reached an even higher terminal temperature of 42.25 °C, because the catalytic cycle’s oxygen supply prevents the hypoxia-induced self-quenching that ordinarily degrades the dye’s performance. Its singlet oxygen quantum yield was approximately 8.9 times higher than free indocyanine green.

Tumor targeting came from a hyaluronic acid coating on the nanoparticle surface, which binds the CD44 receptors abundant on colon cancer cells. Fluorescence microscopy and flow cytometry showed that pretreating cells with free hyaluronic acid to block CD44 significantly reduced uptake, confirming the mechanism. In mice bearing CT26 colon tumors, HILA accumulated progressively in tumor tissue within eight hours of injection and persisted at high levels at 24 hours, while free indocyanine green faded rapidly. Infrared thermal imaging under laser exposure showed HILA-treated tumors heating by roughly 10 °C, the strongest photothermal response among the tested formulations, and ex vivo imaging confirmed selective tumor accumulation.

The therapy’s biological punch was documented in detail. In CT26 cells, HILA depleted intracellular lactate by roughly 60 percent under irradiation and suppressed cell migration from 50.30 percent closure in controls to 19.92 percent at 24 hours. Quantifying each modality’s contribution, the researchers found that in the dark, chemodynamic therapy accounted for 59.7 percent of the killing and starvation for 40.3 percent; under laser irradiation, phototherapy dominated at 72.6 percent, with chemodynamic and starvation effects acting as adjuvants. HILA also collapsed the cells’ antioxidant defenses, cutting glutathione levels by about 75 percent and elevating oxidized glutathione, thereby unleashing a lethal storm of reactive oxygen species from combined photodynamic, photothermal, and chemodynamic sources.

In vivo results sealed the case. Mice treated intravenously with HILA followed by near-infrared irradiation showed near-complete tumor suppression, the lowest excised tumor weights, extensive apoptosis on TUNEL staining, and sharply reduced Ki67 proliferation markers. Hemolysis assays showed less than five percent hemolysis, blood biochemistry revealed no systemic toxicity fourteen days after administration, histology of major organs showed no damage, and body weights remained stable throughout treatment. Pharmacokinetic profiling showed prolonged circulation half-life and mean residence time compared with free drug, extending bioavailability and retention.

The authors describe HILA as a self-amplifying cascade in which lactate depletion, oxygen generation, acidification, glutathione consumption, and light-triggered phototherapy reinforce one another in a positive feedback loop, remodeling the tumor microenvironment while eradicating the cancer within it. By relying on biodegradable, FDA-adjacent components—an approved imaging dye, an enzyme, manganese dioxide, and hyaluronic acid—the platform offers what the researchers call a clinically translatable blueprint for minimally invasive, precision cancer therapy, one that turns the tumor’s own metabolic exhaust into the engine of its destruction.

Subject of Research: A self-sustaining lactate-depleting nanoplatform for multimodal colon cancer therapy

Article Title: Self‐Sustaining Lactate Depletion Nanoplatform Remodels Tumor Microenvironment and Augments Synergistic Photodynamic/Photothermal/Chemodynamic/Starvation Therapy for Eradication of Colon Cancer

Article References: Wang, Y.-E., Zhao, S., Wu, W., Duan, Z., Li, Y., Zeng, X., Hong, L., Chen, Y., Tao, L., Zeng, K., Xiao, C., & Shen, X. (2026). Self‐Sustaining Lactate Depletion Nanoplatform Remodels Tumor Microenvironment and Augments Synergistic Photodynamic/Photothermal/Chemodynamic/Starvation Therapy for Eradication of Colon Cancer. Advanced Science, 13(53), Article e76367. https://doi.org/10.1002/advs.76367

Image Credits: AI Generated

DOI: 10.1002/advs.76367

Keywords: colon cancer, lactate oxidase, manganese dioxide nanoparticles, tumor microenvironment, photodynamic therapy, photothermal therapy, chemodynamic therapy, starvation therapy, indocyanine green, hyaluronic acid targeting, Warburg effect, nanomedicine

The appeal of green synthesis lies in its simplicity. Conventional nanoparticle production often relies on toxic solvents, high temperatures, and chemical reducing agents that leave hazardous residues and carry a heavy environmental footprint. Biogenic methods, by contrast, use phytochemicals as both the reducing and the stabilizing agents. In this case, the team prepared a cold aqueous extract from shade-dried Basella alba leaves and added it dropwise to a dilute solution of potassium permanganate. Phytochemicals in the extract, including phenolics, flavonoids, alkaloids, proteins, and carbohydrates, donated electrons in redox reactions that converted permanganate ions into manganese dioxide, while the same biomolecules adsorbed onto the particle surfaces and capped them, preventing the clumping that plagues many synthetic routes.

The transformation was visible to the naked eye: the pink permanganate solution turned dark brown as the reaction proceeded, a classic signature of manganese dioxide formation. Before synthesis, the researchers had confirmed through qualitative phytochemical screening that the aqueous leaf extract contained alkaloids, phenols, and terpenoids, the molecular workhorses responsible for reduction and stabilization. The plant itself is a nutritional powerhouse, rich in vitamins A and C, folate, manganese, betalain pigments, carotenoids, bioflavonoids, beta-sitosterol, and lupeol, compounds previously linked to antioxidant, antimicrobial, anti-inflammatory, and antiproliferative effects.

Characterization confirmed that the resulting material, dubbed Ba-MnO2-NPs, was genuinely nanoscale and crystalline. Ultraviolet-visible spectroscopy showed a sharp absorption peak at 357 nanometers, consistent with manganese dioxide nanoparticle formation. Fourier-transform infrared spectroscopy revealed the functional groups at work: a broad band at 3421 reciprocal centimeters corresponding to hydroxyl groups from phenolic compounds that served as reducing agents, aliphatic carbon-hydrogen stretches between 2920 and 2850 reciprocal centimeters, a carbonyl band at 1632 reciprocal centimeters pointing to proteins and flavonoids involved in surface stabilization, and strong signals between 1200 and 1000 reciprocal centimeters characteristic of the carbohydrates and polysaccharides acting as capping agents.

Electron microscopy painted a picture of predominantly spherical, slightly agglomerated particles in the range of roughly 200 to 400 nanometers, which the authors classify as zero-dimensional nanostructures based on their geometry. Energy-dispersive X-ray spectroscopy verified the elemental composition, detecting manganese and oxygen as expected. Powder X-ray diffraction displayed four distinct peaks at 2-theta angles of 23, 31, 43, and 65 degrees, confirming the crystalline nature and phase purity of the product. Particle size analysis in aqueous suspension gave an average hydrodynamic diameter of 159.6 nanometers, a figure larger than the dry electron-microscopy measurement because it includes the hydration shell and the layer of adsorbed plant phytochemicals surrounding each particle core.

The biological results were the most eye-catching part of the study. Against Klebsiella pneumoniae, a Gram-negative pathogen notorious for drug resistance, the nanoparticles produced inhibition zones of 4, 9, and 16 millimeters at concentrations of 30, 60, and 90 micrograms respectively, outperforming a 25-microgram ampicillin standard that managed only 9 millimeters. Against the Gram-positive Staphylococcus aureus, the zones grew from 5 to 8 to 23 millimeters across the same concentration range, dwarfing the 8-millimeter zone of the standard drug. Broth micro-dilution assays pinned the minimum inhibitory concentrations at 20 micrograms per milliliter for K. pneumoniae and 40 micrograms per milliliter for S. aureus, potent figures for a plant-derived nanomaterial.

Antioxidant testing using the DPPH free-radical assay showed dose-dependent scavenging, peaking at 67.04 percent inhibition at 250 micrograms per milliliter, compared with 89.19 percent for the ascorbic acid reference. The reported half-maximal inhibitory concentration values place the nanoparticles in a range comparable to other biogenic manganese dioxide materials described in recent literature, including those synthesized with green tea extract, Viola betonicifolia leaf extract, and Gardenia resinifera leaves, all of which showed similar concentration-dependent behavior in radical neutralization and microbial inhibition.

The anticancer findings may prove the most consequential. Using the MTT viability assay on A549 human lung cancer cells, with cisplatin as a positive control, the researchers observed a steep, dose-dependent drop in cell survival. Viability fell from 84.65 percent at 20 micrograms per milliliter to just 25.81 percent at 100 micrograms per milliliter, yielding an IC50 of 70.55 micrograms per milliliter. Microscopy of the treated cultures revealed the hallmarks of programmed cell death: cell shrinkage, elongation, turgidity changes, and the appearance of apoptotic bodies. Because manganese dioxide is considered relatively low in toxicity and biocompatible, the authors suggest these nanoparticles could be candidates for further development against lung cancer, one of the deadliest malignancies worldwide.

The work fits into a broader shift in green chemistry, in which agricultural and medicinal plants serve as renewable nanofactories. Previous studies have shown biogenic manganese dioxide nanoparticles with strong antibiofilm activity, low toxicity toward normal cells, and even the ability to improve chickpea seed germination when formulated with plant root extracts. What distinguishes the new study is the combination of a widely cultivated, edible plant with a full panel of physicochemical characterization and three independent biological assays, providing an unusually complete profile for a single green-synthesized material.

Caveats remain before any clinical translation. All of the results are in vitro, and the road from a microplate assay to a therapeutic agent involves pharmacokinetics, toxicity in animal models, large-scale manufacturing consistency, and regulatory scrutiny. The hydrodynamic size of nearly 160 nanometers, while nanoscale, sits above the conventional 10-to-100-nanometer window, and the authors attribute this to phytochemical capping and drying-induced aggregation, factors that would need careful control in any scaled-up process. Still, the prospect of turning a backyard spinach relative into a sustainable source of antibacterial and anticancer nanomaterials captures the essence of green chemistry: simpler inputs, cleaner reactions, and outputs that could matter to medicine. As antimicrobial resistance escalates and lung cancer continues to claim lives, plant-powered nanoparticles like these offer a low-cost, environmentally benign starting point for the next generation of biomedical materials.

Subject of Research: Green synthesis of manganese dioxide nanoparticles from Basella alba leaf extract and their antibacterial, antioxidant, and anticancer properties

Article Title: Bio-fabrication of sustainable MnO2 nanoparticles using Basella alba L. aqueous extract, its physicochemical characterization and in-vitro biological explorations

Article References: Chidre, P., Shankarappa, V., Bosepalaiah, K., Dharmanaik, C., & Hulikunte Mallikarjunaiah, N. (2026). Bio-fabrication of sustainable MnO2 nanoparticles using Basella alba L. aqueous extract, its physicochemical characterization and in-vitro biological explorations. Discover Green Chemistry, 1(1), Article 35. https://doi.org/10.1007/s44509-026-00039-7

Image Credits: AI Generated

DOI: 10.1007/s44509-026-00039-7

Keywords: green synthesis, manganese dioxide nanoparticles, Basella alba, nanomedicine, antibacterial activity, antioxidant, anticancer, lung cancer A549, DPPH assay, phytochemicals, green chemistry, nanoparticle characterization