Researchers have built a lipid nanoparticle that combines a polymeric carbon nitride semiconductor with the chemotherapy drug cisplatin, and their early studies suggest the platform changes where the drug travels in the body and how effectively it kills cancer cells under illumination. The hybrid particles, described in Discover Nano, self assemble into cubosome structures roughly 150 to 200 nanometers across and, in mice, delivered platinum to the lungs at higher levels than to the liver or kidneys, a distribution pattern that contrasts sharply with the kidney dominated accumulation of free cisplatin. In cell culture, the particles showed little toxicity in the dark but became markedly more lethal to lung, liver, and kidney derived cell lines once exposed to light, consistent with a photodynamic therapy mechanism driven by reactive oxygen species.
The team, led by scientists including Sk Jahir Abbas and Wen-Lung Ma, began with graphitic carbon nitride, a metal free polymeric semiconductor produced by heating melamine above 500 degrees Celsius. Ultrasonic liquid phase exfoliation broke the bulk material into few layered nanosheets measuring about 2.0 nanometers thick, with lateral dimensions between 150 and 250 nanometers. Atomic force microscopy and X-ray diffraction confirmed the exfoliation: the characteristic bulk diffraction peak broadened and weakened, and topographic heights below 3.3 nanometers matched the expected interlayer spacing of three to six individual carbon nitride layers.
To turn these nanosheets into drug carriers, the researchers coupled them with functionalized phospholipids using DSPE-PEG-Mal as a linker, allowing the maleimide group to attach cisplatin and form a lipid carbon nitride cisplatin complex. A one pot self assembly step then integrated this complex with cholesterol for structural integrity, the phospholipid DOPC, the stability enhancing surfactant TPGS, and the core forming polymer PLGA. The final particles, which the authors call LCND nanoparticles, were compared against cisplatin free control particles made by the same route.
Structural characterization revealed a striking morphological transition. Intermediate lipid carbon nitride assemblies were spherical, with an average size near 150 nanometers, but cryogenic electron microscopy of the cisplatin loaded particles showed a cubosome architecture with diameters of 150 to 200 nanometers, suggesting that cisplatin loading reorganizes the internal lipid structure from simple spheres into ordered cubic phases. Dynamic light scattering gave a final particle size of 175 plus or minus 5.9 nanometers, with no significant aggregation after one week of storage. The surface charge settled at minus 0.45 millivolts, a near neutral value the authors note is favorable for extending blood circulation by reducing protein opsonization.
A key functional test concerned light driven chemistry. Under illumination, carbon nitride can generate reactive oxygen species through photosensitization, and electron paramagnetic resonance spectroscopy confirmed this capacity in the final particles. Using the DMPO spin trapping probe, the team detected hydroxyl radicals in aqueous dispersion, accounting for 17.8 percent of the relative signal abundance, and, in methanol, two shorter lived species: hydroperoxyl radicals at 42.6 percent and superoxide radicals at 54.7 percent. Signal intensity increased as irradiation time progressed from one to fifteen minutes, although the loaded particles showed weaker signals than bare carbon nitride nanosheets, which the authors attribute to the semiconductor being buried within the composite core and to charge transfer into the surrounding matrix.
The biodistribution work used healthy male C57BL/6 mice, eight to nine weeks old, injected intravenously and analyzed twelve hours later by ICP-MS. Free cisplatin at doses of 4, 20, and 40 milligrams per kilogram concentrated heavily in the kidneys, reaching mean platinum levels of 5.8, 8.2, and 12.3 micrograms of platinum per gram of tissue, followed by the liver, a pattern consistent with the rapid renal clearance and nephrotoxicity associated with the clinical drug. The nanoparticle formulation at 40 milligrams per kilogram behaved differently: platinum levels were highest in the lungs at 0.09 micrograms per gram, compared with 0.06 in the kidneys, 0.03 in the liver, and 0.012 micrograms per milliliter in plasma, with minimal accumulation in the heart, thymus, spleen, and intestines.
The authors are careful to note that the differences among lung, liver, and kidney levels for the nanoparticles were not statistically significant at the twelve hour time point, so the pulmonary trend is suggestive rather than conclusive. They also emphasize the magnitude of the reduction in off target platinum: kidney levels fell from 5.8 micrograms per gram with free cisplatin at 4 milligrams per kilogram to 0.06 with the nanoparticle formulation, and lung levels from 1.4 to 0.09. Notably, even at the high dose of 40 milligrams per kilogram, the particles did not cause significant weight loss in the mice, and a pharmacokinetic analysis showed prolonged blood circulation from zero to six hours after administration, with a decline by twelve hours. The team also examined plasma lipoprotein fractions and found no significant changes in the size or surface charge of VLDL, LDL, or HDL particles apart from a minor shift in HDL at twenty four hours, supporting vascular compatibility, though comprehensive histopathology and serum chemistry panels remain ongoing investigations.
In vitro, the therapeutic window was mapped across three cell lines: A549 lung adenocarcinoma cells, Tong liver cancer cells, and HEK-293T embryonic kidney cells. Under dark conditions, the half maximal inhibitory concentrations were 176.2 micrograms per milliliter for A549, 139.1 for Tong, and 279.3 for HEK-293T cells, indicating limited inherent toxicity without illumination. When light was applied, significant dose dependent viability losses appeared at concentrations of 50 to 200 micrograms per milliliter for A549 cells and 100 to 200 for Tong and HEK-293T cells. Microscopy showed that illuminated cells developed morphological changes characteristic of apoptosis or necrosis, while cells treated in the dark retained a normal appearance, providing visual evidence that the therapeutic effect is photoactivated.
Additional assays filled out the safety and behavior profile. The empty carrier particles maintained cell viability between 72 and 94 percent across concentrations of 50 to 400 micrograms per milliliter, and the bare carbon nitride nanosheets showed high intrinsic biocompatibility, while free cisplatin displayed its characteristic dose dependent cytotoxicity. Scratch wound healing experiments, run under visible light across a range of concentrations, identified 25 micrograms per milliliter for HEK-293T cells and 1.562 for A549 cells as doses yielding the fastest scratch closure while preserving normal cell viability, observations the authors interpret in terms of effects on cancer cell migration signaling.
The study remains firmly preclinical. The biodistribution work was performed in healthy mice rather than tumor bearing animals, the photodynamic effects were demonstrated only in cell culture, and the authors themselves state that long term clearance and tissue distribution dynamics require further study. What the results do establish is a proof of concept: a cisplatin loaded carbon nitride cubosome that assembles reliably, generates hydroxyl, hydroperoxyl, and superoxide radicals under light, circulates with a modified pharmacokinetic profile that spares the kidneys relative to the free drug, and kills cancer cells selectively upon illumination. If subsequent tumor models confirm both the pulmonary targeting trend and the therapeutic benefit, the platform could offer a route to combining chemotherapy and photodynamic therapy in a single nanoparticle while reducing the systemic toxicity that has long limited cisplatin use.
Subject of Research: Development and preclinical evaluation of a cisplatin loaded carbon nitride cubosome nanoparticle for photodynamic cancer therapy
Article Title: Cubosome integrated with polymeric carbon nitride and cisplatin: in vivo biodistribution and in vitro photodynamic therapy studies
Article References: Abbas, S. J., Mehmood, S., Li, Y.-H., Yesmin, S., Su, C.-K., Sepay, N., Chiang, C.-S., Chang, W.-C., Hung, Y.-C., & Ma, W.-L. (2026). Cubosome integrated with polymeric carbon nitride and cisplatin: in vivo biodistribution and in vitro photodynamic therapy studies. Discover Nano, 21(1), Article 568. https://doi.org/10.1186/s11671-026-05076-6
Image Credits: AI Generated
DOI: 10.1186/s11671-026-05076-6
Keywords: cubosomes, carbon nitride, cisplatin, photodynamic therapy, nanoparticles, biodistribution, drug delivery, reactive oxygen species, lung cancer, ICP-MS, C57BL/6 mice, nanomedicine
News Source: Denise Maddox. (October 29, 2026). Research report: Cubosome integrated with polymeric carbon nitride and cisplatin: in vivo biodistribution and in vitro photodynamic therapy studies. Scienmag.
