The photothermal effect induces M1 macrophage-derived TNF-α-type exosomes to inhibit bladder tumor growth

Bladder cancer presents a significant challenge for patient treatment and prognostic health due to its high recurrence and metastasis. Nanoparticle-based photothermal therapy offers a potential solution, as it can achieve thermal ablation of tumors through photothermal conversion, modulate cytokine and exosome secretion from macrophages to assist in treatment. Herein, a system that integrates gold-manganese nanomaterials and engineered macrophage-derived exosomes for the synergistic treatment of bladder tumors was developed. We encapsulated MnO₂ on the surface of sea-urchin-like Au nanoclusters (AuNCs) to form a nanocomposite with a shell-and-core structure (Au@MnO₂), effectively enhancing its stability and photothermal conversion efficiency. In vitro experiments showed that Au@MnO₂ induced polarization of macrophages to secrete cytokines (e.g., TNF-α, iNOS, etc.) and TNF-α-rich exosomes of the M1 phenotype when exposed to near-infrared light. This M1 phenotype, combined with the nano-photothermal effect, significantly inhibited the proliferation of bladder tumor cells, and promoted apoptosis and cycle blockade. RNA sequencing revealed significant regulation of inflammation-related genes and pathways, including TNF, NF-κB, and cytokine receptor pathways, both in M1 macrophages and their exosomes. In vivo experiments confirmed that engineered macrophages combined with nano-photothermal effect inhibited subcutaneous tumor growth in mice and reduced the macrophage CD206/CD86 ratio in tissues. This study highlights the promise of engineered macrophages combining cytokines, M1-Exo, and the photothermal effects of Au@MnO₂ to achieve synergistic treatment for bladder cancer.