Self-Propelled Nanoreactors for Enhanced Cascade Catalytic Cancer Therapy through NIR-II Fluorescence Imaging-Guided Readministration

The limited penetration depth of nanoreactors within tumors and the inaccurate selection of the optimal timing for readministration significantly restrict the efficacy of cascade catalytic therapy. Therefore, the development of nanoreactors with strong penetration capabilities into tumor tissues and precise readministration recognition systems is of great importance for improving the therapeutic outcomes of cancer treatment. Herein, a self-propelled nanoreactor (designated as DSFGC) is developed. Composed of near-infrared-II fluorescence nanoparticles, a peroxidase (POD)-like nanozyme, and asymmetric functionalized modifications of catalase (CAT) and glucose oxidase (GOx), this nanoreactor is designed to enhance tissue penetration capabilities and identify the optimal readministration timing, thus promoting cascade catalytic therapy efficacy. In tumors, the overexpressed H₂O₂ is catalytically decomposed into O₂ by CAT. This process facilitates the penetration of nanoreactors into deep tumor tissues and acts as an oxygen source to enhance the ability of GOx to catalytically consume glucose, yielding gluconic acid and supplying H₂O₂. The generated gluconic acid can boost the catalytic activity of the POD-like nanozyme and increase the production of ^•OH. Moreover, by leveraging the information obtained from near-infrared-II fluorescence imaging to determine the optimal time for readministration, the cascading catalytic therapeutic effects of starvation therapy and chemodynamic therapy can be augmented.