Platinum-Coordinated Engineered Nanoreactors with O₂ Self-Amplificationand On-Demand Cascade Chemo-Drug Synthesis for Self-Reinforcing Hypoxic Oncotherapy

Abstract

How to efficiently synthesize toxic chemo-drugs in the hypoxia tumor microenvironment still faces a huge challenge. Herein, we have tailored engineered vehicle-free nanoreactors by coordination-driven co-assembly of photosensitizer indocyanine green (ICG), transition metal platinum (Pt), and nontoxic 1,5dihydroxynaphthalene (DHN) to self-amplify O 2 and cascade chemo-drug synthesis in tumor cells for self-reinforcing hypoxic oncotherapy. Once vehicle-free nanoreactors are internalized into tumor cells, they show a serious instability that results in rapid disassembly and on-demand drug release under the stimuli of acidic lysosome and laser radiation. Notably, the released Pt can efficiently decompose the endogenous hydrogen peroxide (H 2 O 2 ) into O 2 to alleviate tumor hypoxia, which is conducive to enhancing the photodynamic therapy (PDT) efficiency of the released ICG. Complementarily, a large amount of the 1 O 2 generated by PDT can efficiently oxidize the released nontoxic DHN into the highly toxic chemo-drug juglone. Therefore, such vehicle-free nanoreactors can achieve intracellular on-demand cascade chemo-drug synthesis and self-reinforce photochemotherapeutic efficacy on the hypoxic tumor. On the whole, such a simple, flexible, efficient, and nontoxic therapeutic strategy will broaden the study of on-demand chemo-drug synthesis and hypoxic oncotherapy.

Engineering Self-Assembled Nanomedicines Composed of Clinically Approved Medicines for Enhanced Tumor Nanotherapy

“…To achieve the high performance and non-side effects of the composite nanosystems, it is imperative to construct biocompatible nanoscale carriers for loading small molecular chemotherapeutic drugs [ 21 , 22 , 23 ], photosensitizers [ 24 , 25 , 26 ], and other functional molecules [ 27 , 28 ]. The broad reports have shown the application potential of diverse nanosystems, including IrO x - [ 29 ], Fe 3 O 4 - [ 30 , 31 ], and MOF-based nanocarriers [ 32 ] loading with doxorubicin (DOX) [ 33 ], curcumin [ 34 ], and fluorouracil [ 35 ].…”