A Self-Enhancing Poly(o-phenylenediamine)@Glucose Oxidase Nanoplatform for ATP-Modulated In Vitro Photothermal Therapy.

The heat shock protein 70 (HSP70)-mediated heat shock program enhances cellular thermotolerance and limits the efficacy of photothermal therapy (PTT) by driving adaptive cellular stress responses. To address this challenge, we report a novel nanoplatform that integrates poly(o-phenylenediamine) (PoPD) with glucose oxidase (GOx). Upon near-infrared (NIR) laser irradiation, PoPD@GOx exhibits pH-responsive photothermal performance. Concurrently, GOx-mediated glucose oxidation induces adenosine triphosphate (ATP) depletion, which suppresses the HSP70-mediated adaptive heat shock program and thereby sensitizes tumor cells to photothermal injury. Furthermore, photothermal heating accelerates the GOx catalytic activity, and the generated gluconic acid further acidifies the microenvironment surrounding PoPD@GOx, in turn enhancing photothermal conversion and forming a self-enhancing positive-feedback loop. Overall, this work establishes a metabolic intervention strategy to overcome thermotolerance in photothermal cancer therapy.