g-C₃N₄-based smart nanocatalysts for photocatalytic cancer therapy: mechanisms, surface engineering, and therapeutic applications

Abstract Cancer remains one of the leading causes of mortality worldwide, necessitating the development of more precise and effective therapeutic strategies. Graphitic carbon nitride (g-C₃N₄) has emerged as a highly promising metal-free semiconductor nanomaterial for photocatalytic cancer therapy owing to its tunable bandgap (~2.7 eV), favorable biocompatibility, chemical stability and large surface area. Recent advances in nanotechnology and surface engineering have transformed g-C₃N₄ from a conventional photocatalyst into a multifunctional nanotheranostic platform for multimodal cancer treatment. This review provides a comprehensive and up-to-date overview of g-C₃N₄-based nanocatalysts, covering photocatalytic mechanisms, engineering strategies, therapeutic applications, biosafety and translational prospects. Under light irradiation, g-C₃N₄ generates reactive oxygen species (ROS) through photoinduced electron–hole separation, triggering oxidative stress-mediated cancer cell death through multiple regulated and non-regulated cell-death pathways, including apoptosis, ferroptosis, necrosis, and, in specific engineered systems, cuproptosis. Advanced engineering strategies including heteroatom doping, heterojunction construction, oxygen vacancy engineering, noble metal decoration and biomimetic surface functionalization have been employed to improve charge separation, extend light responsiveness toward the NIR region, enhance ROS generation, and facilitate tumor targeting. This review highlights recent progress in multimodal therapeutic approaches integrating photodynamic therapy (PDT), photothermal therapy (PTT), chemodynamic therapy (CDT), drug delivery, gas therapy, immunotherapy and nanozyme-mediated catalytic therapy. Emerging g-C₃N₄-based nanozymes with multi-enzyme activities (OXD, POD, CAT, GSHOx, and SOD), together with bioimaging-guided theranostic systems, further expand the therapeutic potential of these nanoplatforms. Finally, key challenges including limited light penetration, hypoxic tumor microenvironment, elevated glutathione levels, biosafety concerns and clinical translation barriers are critically discussed. This review highlights the substantial potential of g-C₃N₄-based nanoplatforms for next-generation precision oncology and clinical translation.