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 MoS(2)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 H(2)O(2)can markedly boost the subordinate peroxidase-like catalytic efficacy of nano-sized MoS2, yielding abundant highly toxic hydroxyl radicals ((OH)-O-center dot) for nanocatalytic therapy. Meanwhile, MoS(2)can also deplete glutathione (GSH) to reduce the consumption of (OH)-O-center dot. Bothin vitroandin vivoresults demonstrated that the MoS2@CGTC NCR performed well in suppressing tumor growthviaself-enhancing chemo-catalytic therapy. This work highlights the use of self-assembled NCRs for enhanced tumor synergetic therapyviaTME regulation.