Glucose-responsive cascaded nanocatalytic reactor with self-modulation of the tumor microenvironment for enhanced chemo-catalytic therapy

Tumor microenvironment (TME)-mediated nanocatalytic therapy has been deemed as a promising strategy for improving the effectiveness of tumor therapy. Herein, we construct a glucose-responsive cascaded nanocatalytic reactor (MoS2@CGTC NCR) which co-loads glucose oxidase (GOx) and chemotherapeutic drug tirapazamine (TPZ) on the surface of the MoS2 nanozyme carrier for modulating the TME to achieve self-enhanced chemo-catalytic therapy. Based on the intratumoral ultrahigh glucose concentration, the MoS2@CGTC NCR can persistently regulate the TME through oxidizing glucose to produce gluconic acid and H2O2, while rapidly depleting oxygen to activate the chemotherapeutic. Subsequently, the self-supplied H+ and H2O2 can markedly boost the subordinate peroxidase-like catalytic efficacy of nano-sized MoS2, yielding abundant highly toxic hydroxyl radicals (OH) for nanocatalytic therapy. Meanwhile, MoS2 can also deplete glutathione (GSH) to reduce the consumption of OH. Both in vitro and in vivo results demonstrated that the MoS2@CGTC NCR performed well in suppressing tumor growth via self-enhancing chemo-catalytic therapy. This work highlights the use of self-assembled NCRs for enhanced tumor synergetic therapy via TME regulation.