ZIF-90-PQ-based cascade nanoplatform for multimodal cooperative treatment of breast cancer.

Owing to the complexity of the tumor microenvironment, monotherapy often suffers from inherent limitations and fails to achieve satisfactory antitumor efficacy. Therefore, multimodal collaborative therapy has become a trend. In this study, CP@ZIF-PQ/Ce6 NPs, a ZIF-90-based multimodal nanosystem loaded with copper peroxide (CP) nanoparticles, the autophagy inhibitor primaquine phosphate (PQ) and the photosensitizer Ce6, were developed. This nanosystem enables the integration of photodynamic therapy (PDT), chemodynamic therapy (CDT), oxygen generation, and autophagy inhibition. Through the combined therapeutic effects of PDT/CDT/O2 generation/autophagy inhibition, CP@ZIF-PQ/Ce6 NPs enhance the production of reactive oxygen species(ROS), alleviate tumor hypoxia, and block the autophagy-mediated protective pathway in tumor cells. Moreover, the nanosystem exhibits dual pH- and ATP-responsive properties, allowing tumor microenvironment-triggered drug release. CP@ZIF-PQ/Ce6 NPs successfully integrate PDT, CDT, oxygen-generating therapy, and autophagy inhibition, demonstrating potent antitumor activity and favorable biocompatibility both in vitro and in vivo. This study provides an innovative strategy and experimental evidence for multimodal collaborative antitumor therapy to overcome the limitations of monotherapy imposed by the tumor microenvironment.