Engineered mesoporous carbon spheres with tailored pore structures for improved photothermal-chemotherapy

Carbon-based materials have gained significant attention in anticancer treatment because of their exceptional biocompatibility, yet critical challenges persist in establishing definitive correlations between their porous structures and functional performance. We report the use of a silica template to guide pore formation in the design of mesoporous carbon spheres (mC) with tailored pore structures for improved combined photothermal-chemotherapy. The mesopore size of mC has been adjusted by kinetic control of the resin polymerization and silica hydrolysis. Structural characterization showed that 4.4 nm mesopores enabled an exceptional gemcitabine loading of 228 mg g−1 and a sustained pH/thermal dual-responsive release with > 70% drug release under near-infrared (NIR) irradiation. Finite element analysis demonstrated pore size-dependent heat transfer dynamics, with the improved mC achieving a superior photothermal conversion efficiency of 62% by a combination of N-doping and defect engineering. In vitro evaluations confirmed outstanding biocompatibility with > 95% cell viability at 200 μg mL−1 and potent tumor suppression in pancreatic and biliary cancer models with an ~ 5% cell viability at 25 μg mL−1 where combined therapy showed a 3.7-fold increased cytotoxicity over monotherapy. The improved structure of mC facilitated cascade therapeutic effects with enhanced tumor permeability derived from NIR-triggered hyperthermia and prolonged therapeutic exposure due to pH-responsive drug release. This pore engineering strategy establishes a structure-function process for next-generation theranostic platforms, addressing the critical limitations of conventional pancreatic and biliary cancer therapies through spatiotemporal control of multimodal treatment.