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 enhanced 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.