Enhancing Photodynamic and Chemodynamic Therapy Efficacy through a Novel ROS-Amplifying Therapeutic Platform for Breast Cancer Treatment

Abstract

Suboptimal reactive oxygen species (ROS) production in photodynamic therapy (PDT) and chemodynamic therapy (CDT) due to tumor antioxidants and H₂O₂ constraints poses a challenge to their therapeutic efficacy. To address this, our study introduces GOx@MPN@Gel, a novel PDT/CDT platform that integrates glucose oxidase (GOx), luteolin, iron ions, a traditional Chinese medicine-inspired metal-phenolic network (MPN), and hydrogel (Gel) carriers to enhance ROS generation. Experimental results demonstrate GOx@MPN@Gel heightened acid sensitivity, robust GOx activity, and significant ROS production. Both in vitro and in vivo tests validate its therapeutic potential. Within the tumor microenvironment, GOx@MPN@Gel effectively elevates H₂O₂ levels for CDT, producing cytotoxic hydroxyl radicals (·OH), and upon near infrared (NIR) light exposure, its porphyrin component triggers potent PDT effects, generating additional ROS. This synergistic approach significantly enhances antitumor efficacy. The platform's unique design, combining acid-responsive degradation and PDT/CDT synergy, offers a promising personalized treatment strategy for breast cancer.