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Regulating redox homeostasis in tumor cells and exploiting oxidative stress to damage tumors is an efficacious strategy for cancer therapy. However, the strengths of organic nanomaterials within this strategy are often ignored. In this work, a light-triggered reactive oxygen species (ROS) damaging nanoamplifier (IrP-T) was developed for enhanced photodynamic therapy (PDT). The IrP-T was fabricated with an amphiphilic iridium complex and a MTH1 inhibitor (TH287). Under green light stimulation, IrP-T catalyzed the oxygen in cells to generate ROS for realizing oxidative damage; meanwhile, TH287 increased the accumulation of 8-oxo-dGTP, further strengthening oxidative stress and inducing cell death. IrP-T could maximize the use of a small amount of oxygen, thus further boosting the efficacy of PDT in hypoxic tumors. The construction of nanocapsules provided a valuable therapeutic strategy for oxidative damage and synergizing PDT. [ABSTRACT FROM AUTHOR]

[Display omitted] • LTA zeolites loaded C 3 N 4 system could enhance ROS production efficiency via photocatalytic. • C 3 N 4 contributes to high surface conductivity and high drug loading. • UCNPs-C 3 N 4 -Ce6 system could relief the tumour hypoxia. • UCNPs-C 3 N 4 -Ce6 system could induce autophagic cell death with minimal negative side effects. • PDT and SDT was proved capable of maximizing the ROS yield. Reactive oxygen species (ROS) production efficiency, tumor microenvironment hypoxia relief, and autophagy-induced cell death with minimal negative effects are considered the main objectives to achieve more efficient tumor treatment. However, realizing highly effective cancer treatment under hypoxia relief with a cell autophagy model based on suitable biomaterials is still a challenge. Herein, a biosafe upconversion nanomaterial based on Linde Type A (LTA) zeolites loaded with carbon nitride (C 3 N 4) photocatalyst and chlorin e6 (Ce6) was developed as a rationally regulated photocatalytic system and multimodal tumor therapeutic platform. C 3 N 4 contributes to stability, tumor hypoxia relief, high surface conductivity and high drug-loading. Remarkably, photodynamic therapy (PDT) and sonodynamic therapy (SDT) were proven capable of maximizing the ROS yield to obtain highly tumor therapeutic outcomes. Photothermal conversion efficiency was 46.72%. Furthermore, internalized nanomaterials can result in tumor inhibition through cell autophagy. The as-developed system shows a promising potential in the multimodal cancer therapeutics. [ABSTRACT FROM AUTHOR]

[Display omitted] • Smart g-C3N4/Ce6 nanohybrids was developed as a rational multifunctional nanoplatform for tumor therapy. • The metal-free g-C3N4/Ce6 photocatalyst boosted photo/sonodynamic ROS generation and acute tumor inactivation. • Enhanced maturation of DC cells and long-term cancer immunotherapy over g-C3N4/Ce6 was also verified. • The 2D g-C3N4/Ce6 platform with good biocompatibility and expansibility has good potential in biomedicine. 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-C 3 N 4 /Ce6) nanohybrids for use as a rational multifunctional nanoplatform in which the unstable sono-photosensitizer Ce6 was immobilized by unique protonated g-C 3 N 4 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-C 3 N 4 /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-C 3 N 4 /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-C 3 N 4 /Ce6 system, this work highlights the promise of 2D g-C 3 N 4 -based multifunctional nanostructures designed as smart metal-free nanoplatforms for cancer theranostics. [ABSTRACT FROM AUTHOR]