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

Abstract

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.