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 (MoS 2 @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 MoS 2 @CGTC NCR can persistently regulate the TME through oxidizing glucose to produce gluconic acid and H 2 O 2 , 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 MoS 2 , yielding abundant highly toxic hydroxyl radicals (&z.rad;OH) for nanocatalytic therapy. Meanwhile, MoS 2 can also deplete glutathione (GSH) to reduce the consumption of &z.rad;OH. Both in vitro and in vivo results demonstrated that the MoS 2 @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. Here, a glucose-responsive cascaded nanocatalytic reactor was proposed for enhanced synergetic chemo-catalytic therapy through persistent TME self-modulation.