The research team, led by authors including Guangwei Zheng, Peiyuan Wang and Tao Xu, built their nanocarrier, dubbed cSiCe&ICG, through a lamellar micelle spiral self-assembly process conducted in a biphasic oil-water stratification system. In this elegant one-pot synthesis, the silicate precursor tetraethyl orthosilicate dissolved in cyclohexane sits atop an aqueous phase containing the surfactant template hexadecyltrimethylammonium p-toluenesulfonate and triethanolamine as a catalyst. Under continuous stirring, lamellar micelles co-assemble at the interface into helical, multi-shelled mesoporous silica nanospheres roughly 170 nanometers in diameter. The cerium precursor, added six hours into the reaction, hydrolyzes into cerium oxide nanogranules that anchor both to the silica surface and within the framework, giving a cerium-to-silicon weight ratio of 2:7. Transmission electron microscopy revealed that the resulting particles exist as mixtures of clockwise and counterclockwise helical configurations, with interlayer spacings of about 3 nanometers and outer gaps exceeding 10 nanometers, a texture that proved critical for what came next.

Chirality, the property of existing as mirror-image forms, is ubiquitous in biology, where amino acids and phospholipids occur almost exclusively in the L-configuration and sugars in the D-form. The researchers reasoned that importing chirality into an inorganic nanoreactor could confer advantages that symmetric particles lack. Their comparisons against a conventional dendritic mesoporous silica counterpart, mSiCe&ICG, bore this out repeatedly. The chiral channels promoted monomeric dispersion of the loaded ICG rather than the fluorescence-quenching J-aggregates that form in symmetric pores, and the spiral architecture with fewer open ends accelerated molecular motion. The practical consequence was striking: after 24 hours under ambient light, the NIR-II fluorescence of cSiCe&ICG was 21-fold stronger than free ICG, while the achiral mSiCe&ICG reached only 14-fold. The chiral particles also degraded faster in mildly acidic conditions, disintegrating within 24 hours at pH 6.5 while remaining intact at physiological pH 7.4, a built-in safety feature that confines drug release to the tumor microenvironment.

The imaging gains address a well-known weakness of ICG, the only NIR fluorophore in routine clinical use. Although ICG emits in both the first and second near-infrared windows, it suffers from rapid bloodstream clearance, poor tumor retention, strong binding to serum albumin, and rapid photodegradation under the very lasers used to excite it. Encapsulated within the chiral mesopores, ICG retained more than 90 percent of its initial fluorescence after 72 hours in serum with no detectable leakage, and the loading efficiency reached 20.61 percent. In tumor-bearing mice, the chiral probe painted a clear tumor outline from 6 to 12 hours after intravenous injection, while free ICG produced negligible tumor signal. Quantitative measurements of cerium ions by inductively coupled plasma optical emission spectroscopy confirmed far greater tumor accumulation for the chiral formulation, and the tumor-to-background ratio peaked at approximately 10.8 times that of free ICG at the 12-hour mark, which the team selected as the optimal imaging and treatment window.

The therapeutic half of the platform exploits the redox versatility of cerium, which shuttles between Ce4+ and Ce3+ oxidation states. X-ray photoelectron spectroscopy showed a Ce3+ to Ce4+ ratio of roughly 4:3, favorable for Fenton-like catalysis. In the acidic tumor milieu, the cerium oxide nanozymes decompose hydrogen peroxide into hydroxyl radicals while simultaneously depleting glutathione, the cell’s principal antioxidant, by more than 85 percent after 36 hours at pH 6.5. This dual action strips away the tumor’s chemical defenses and floods the cytoplasm with reactive oxygen species. The photothermal component then acts as an amplifier: under 808-nanometer laser irradiation, the ICG-loaded nanoreactor heated a 200 microgram per milliliter solution to 60.3 degrees Celsius in five minutes, compared with 47.9 degrees for free ICG and 30.5 degrees for saline, with a light-to-heat conversion efficiency of approximately 58.8 percent and stable performance across repeated laser cycles.

Cell culture experiments with MB49 bladder cancer cells demonstrated how heat and catalysis conspire. Confocal microscopy showed that cellular uptake of the chiral particles peaked at eight hours and significantly exceeded that of the achiral control, with the chiral probes entering cells through both caveolin- and clathrin-mediated endocytosis rather than the single caveolin pathway used by symmetric particles. When laser irradiation was added, intracellular reactive oxygen species, detected by the DCFH-DA probe, rose dramatically above every control group, and hydroxyphenyl fluorescein staining confirmed a surge of hydroxyl radicals. JC-1 staining revealed severe mitochondrial membrane depolarization in the treated cells, and flow cytometry quantified approximately 62.5 percent apoptotic cell death in the combined-treatment group. Notably, even at the highest tested concentration of 300 micrograms per milliliter, 93.8 percent of normal human umbilical vein endothelial cells remained viable, reflecting the particle’s dependence on acidic conditions for activation.

The surgical navigation experiments delivered perhaps the most clinically resonant results. Twelve hours after injection, NIR-II fluorescence clearly delineated tumor margins in mice with subcutaneous bladder tumors. Surgeons first removed the main tumor mass under white light, then scanned the surgical bed with the NIR-II system, which flagged residual fluorescent tissue that was subsequently resected. Histological examination found no remaining cancer cells in the fluorescence-guided group, whereas tumors removed under white light alone left residual tumor cells behind. Thirty days after surgery, bioluminescence imaging detected recurrence in every mouse operated under white light, but no signal in the fluorescence-guided group. Survival at 60 days reached 80 percent for the NIR-II-guided cohort compared with just 10 percent for the white-light group, a difference the authors attribute to the chiral probe’s superior tumor penetration, retention, and protein corona formation, which extended its blood circulation half-life to 11.7 hours versus 7.4 hours for the achiral version.

In the therapeutic efficacy study, mice receiving the full combination of cSiCe&ICG plus laser irradiation showed the strongest tumor regression over a 21-day treatment period, outperforming the achiral formulation and the cerium-only groups. Histological staining with hematoxylin and eosin, TUNEL, and Ki67 confirmed extensive tumor destruction, widespread apoptosis, and suppressed proliferation in the combination group. Biosafety assessments were encouraging: treated mice maintained stable body weights, blood chemistry and hematological indices stayed within healthy ranges, and cerium and silicon ions were almost completely cleared from the liver, spleen, and lungs within 28 days. Serum levels of inflammatory cytokines including IL-10, TNF-alpha, and IFN-gamma showed no significant fluctuations, and the particles’ rapid biodegradation under acidic conditions further limited off-target exposure.

The authors report that this represents the first facile fabrication of a chiral cerium oxide nanoreactor for precise, synergistic treatment of malignant tumors, and the design philosophy carries broader implications. By demonstrating that chirality can simultaneously enhance cellular uptake, fluorescence output, catalytic efficiency, and biodegradation, the study suggests that mirror-image engineering of inorganic nanomaterials is a powerful, largely untapped lever for cancer nanomedicine. The platform’s reliance on clinically accepted ICG, a straightforward one-pot synthesis, and tumor-triggered disassembly positions it favorably for translational development. Considerable work remains before such nanoreactors reach the operating room, including larger animal models, orthotopic bladder tumors, and formal toxicity studies, but the convergence of image-guided surgery with photothermally reinforced chemodynamic therapy offers a compelling template for tackling the residual disease that drives bladder cancer recurrence.

Subject of Research: A chiral cerium-doped mesoporous silica nanoreactor for fluorescence-guided surgery and photothermal-chemodynamic therapy of bladder cancer

Article Title: Chiral cerium doped nanoreactor-mediated bladder carcinoma reinforced ablation via fluorescence imaging navigated surgery along with photothermal strengthened ROS storm

Article References: Zheng, G., Wang, A., Du, Y., Qin, C., Song, Y., Wu, J., Luo, X., Liu, X., Wang, P., & Xu, T. (2026). Chiral cerium doped nanoreactor-mediated bladder carcinoma reinforced ablation via fluorescence imaging navigated surgery along with photothermal strengthened ROS storm. Materials Today Bio, 41, Article 103746. https://doi.org/10.1016/j.mtbio.2026.103746

Image Credits: AI Generated

DOI: Not provided

Keywords: bladder cancer, chiral nanoparticles, cerium oxide, mesoporous silica, indocyanine green, NIR-II fluorescence imaging, photothermal therapy, chemodynamic therapy, reactive oxygen species, image-guided surgery, nanoreactor, tumor microenvironment