Nanozyme-nanoclusters in metal–organic framework: GSH triggered Fenton reaction for imaging guided synergistic chemodynamic-photothermal therapy

It is of great significance to design functional nanomaterials with specific response to tumor microenvironments (TMEs), so as to achieve accurate imaging and efficient treatment of tumor. In this work, a TME-activated biomimetic nanocomposite with dual imaging capabilities of turn-on fluorescence imaging and photothermal imaging was constructed for high-sensitivity sensing of glutathione (GSH) and self-enhanced photothermal/chemodynamic synergistic therapy. The nanocomposite was designed by loading nanozyme MnO2 and luminol gold nanoclusters on ZIF-8 (Z-M-LA), which was then coated with 4T1 cell membrane (Z-M-LA@CM). The biomimetic membrane decoration was used to escape immune clearance and maintain good biocompatibility and targeting ability. The fluorescence of luminol gold nanoclusters quenched by MnO2 can be recovered in vivo through MnO2 degradation by GSH, which enables the TME-activated visualization of tumor. Simultaneously, MnO2 shows peroxidase-like activity after being degraded by GSH and the released Mn2+ can catalyze H2O2 to generate abundant hydroxyl radicals (·OH) to realize self-enhanced photothermal/chemodynamic synergistic therapy. Furthermore, Z-M-LA@CM was also investigated to induce immune effect in vivo and it exhibited good pH-responsive degradation behavior, which could remain stable under alkaline conditions (pH = 7.4) and be degraded in acidic solutions (pH = 5.6). These properties make Z-M-LA@CM an appealing biodegradable nanotherapeutic agent for tumor precise diagnosis and therapy.