The clinical application of stimulator of interferon genes (STING) agonists in cancer immunotherapy has been limited by inefficient systemic delivery, off-target toxicity and the immunosuppressive tumor microenvironment. In this study, we developed a multifunctional nanoplatform featuring a hollow manganese dioxide (H-MnO₂) as a core sequentially coated with polydopamine (PDA) and graphitic carbon nitride (g-C₃N₄) layers, termed as HMPC. HMPC mediates antitumor immunity through three coordinated mechanisms. (i) H-MnO₂ decomposes in response to glutathione (GSH), releasing Mn²⁺ to activate STING pathway, and catalyzing H₂O₂ to produce oxygen, effectively alleviating hypoxia-mediated immunosuppression in the tumors. (ii) The hollow structure enhances electron transfer between g-C₃N₄ and PDA, enabling robust reactive oxygen species (ROS) generation under 660 nm irradiation, which synergizes with Mn²⁺-mediated Fenton-like reactions for cooperative ROS amplification. (iii) The ROS burst potently induces immunogenic cell death (ICD), releasing double-stranded DNA (dsDNA) that cooperates with Mn²⁺ to sustain STING activation. In vivo, HMPC triggers a STING-dependent immune signaling cascade, enhancing tumor infiltration of CD8⁺ T cells, CD4⁺ T cells, natural killer (NK) cells, and M1-type macrophages, thereby promoting tumor eradication. By spatiotemporally coupling STING activation with photodynamic therapy, HMPC demonstrates multimodal responsiveness and synergistic efficacy, offering a potential strategy to overcome current barriers in cancer immunotherapy.

Methicillin-resistant Staphylococcus aureus (MRSA) presents a significant challenge in wound infection treatment due to its antibiotic resistance and biofilm formation. To address this, we utilized Escherichia coli (Ec) as a carrier to deliver lysozyme (LYZ) and adsorb the photosensitizer indocyanine green (ICG), resulting in the Ec-LYZ-ICG multi-functional antimicrobial platform. Since both Ec and MRSA are bacteria, this platform can act as a “spy”, evading the immune surveillance of MRSA and effectively penetrating infection sites. Upon exposure to 808 nm laser irradiation, Ec-LYZ-ICG utilizes the synergistic effects of photothermal therapy (PTT) and photodynamic therapy (PDT) induced by ICG, which ruptures Ec membrane and releases LYZ. The combined PTT and PDT directly damage MRSA, while LYZ further hydrolyzes MRSA. This strategy, with its “spy-like” camouflage and penetration abilities, overcomes MRSA’s antibiotic resistance and immune evasion, providing new insights and approaches for the precise treatment of MRSA infections.

Dual inhibition of glycolysis and oxidative phosphorylation (OXPHOS) can break the metabolic plasticity of cancer cells to inhibit most energy supply and lead to effective cancer therapy. However, the pharmacokinetic difference among drugs hinders these two inhibitions to realize a uniform temporal and spatial distribution. Herein, we report an aptamer-based artificial enzyme for simultaneous dual inhibition of glycolysis and OXPHOS, which is constructed by arginine aptamer modified carbon-dots-doped graphitic carbon nitride (AptCCN). AptCCN can circularly capture intracellular arginine attribute to the specific binding ability of arginine aptamers to arginine, and further catalyze the oxidation of enriched arginine to nitric oxide (NO) under red light irradiation. In vitro and in vivo experiments showed that arginine depletion and NO stress could inhibit glycolysis and OXPHOS, leading to energy blockage and apoptosis of cancer cells. The presented aptamer-based artificial enzyme strategy provides a new path for cell pathway regulation and synergistic cancer therapy.

The promising potential of photodynamic therapy (PDT) has fueled the development of minimally invasive therapeutic approaches for cancer therapy. However, overcoming limitations in PDT efficacy in the hypoxic tumor environment and light penetration depth remains a challenge. We report the engineering of tungsten carbide nanoparticles (W₂C NPs) for 1, 064 nm laser-activated dual-type PDT and combined theranostics. The synthesized W₂C NPs allow the robust generation of dual-type reactive oxygen species, including hydroxyl radicals (type Ⅰ) and singlet oxygen (type Ⅱ), using only single 1, 064 nm laser activation, enabling effective PDT even in the hypoxic tumor environment. The W₂C NPs also possess high photothermal performance under 1, 064 nm laser irradiation, thus enabling synergistically enhanced cancer therapeutic efficacy of PDT and photothermal therapy. Additionally, the photoacoustic and X-ray computed tomography bioimaging properties of W₂C NPs facilitate the integration of tumor diagnosis and therapy. The developed W₂C based theranostic nanoagents increase the generation of reactive oxygen species in hypoxic tumors, improve the light penetration depth, and facilitate combined photothermal therapy and photoacoustic/computed tomography dual-mode bioimaging. These attributes could spur the exploration of transition metal carbides for advanced biomedical applications.