Protonated 2D carbon nitride sensitized with Ce6 as a smart metal-free nanoplatform for boosted acute multimodal photo-sono tumor inactivation and long-term cancer immunotherapy

Multifunctional nanoplatforms for the early diagnosis and precise treatment of cancers have been widely explored in nanomedicine but still suffer from complex material design and intrinsic incompatibility among various biomaterial components. Moreover, a rational mode of tumor therapy that considers the effect of immune adjuvants while promoting long-term cancer immunotherapy is highly needed. Herein, we developed smart metal-free two-dimensional (2D) graphitic carbon nitride/chlorin e6 (g-C3N4/Ce6) nanohybrids for use as a rational multifunctional nanoplatform in which the unstable sono-photosensitizer Ce6 was immobilized by unique protonated g-C3N4 nanosheets. The 2D nanomedicine system shows excellent stability, biocompatibility, ideal near-infrared absorption, an optimized band structure and charge separation ability. As a result, the g-C3N4/Ce6 nanoplatform remarkably combines photodynamic, photothermal and sonodynamic therapies. Additionally, importantly, dead tumor cells can serve as tumor-associated antigens to support in vivo immune stimulation, and the mild photothermal effect greatly promoted the immune adjuvant effect of the g-C3N4/Ce6 nanohybrids, resulting in the greatly enhanced maturation of DC cells and long-term cancer immunotherapy. No obvious long-term toxicity of the nanocomposites was found at the injected dose. Given the great general drug loading potential and adaptability of the g-C3N4/Ce6 system, this work highlights the promise of 2D g-C3N4-based multifunctional nanostructures designed as smart metal-free nanoplatforms for cancer theranostics.