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Breast cancer is one of the most common malignant tumors in women. The existence of multiple breast cancer subtypes often leads to chemotherapy failure or the development of drug resistance. In recent years, photodynamic therapy has been proven to enhance the sensitivity of tumors to chemotherapeutic drugs. Porphyrin-based metal–organic framework (MOF) materials could simultaneously be used as carriers for chemotherapy and photosensitizers in photodynamic therapy. In this paper, doxorubicin hydrochloride (DOX) was loaded in porphyrin MOFs, and the mechanism of the synergistic effect of the DOX carriers and photodynamic therapy on breast cancer was investigated. In vitro and in vivo experiments have shown that MOFs could prolong the residence time of DOX in tumor tissues and promote the endocytosis of DOX by tumor cells. In addition, adjuvant treatment with photodynamic therapy can promote breast cancer tumors to resensitize to DOX and synergistically enhance the chemotherapy effect of DOX. Therefore, this study can provide effective development ideas for reversing drug resistance during breast cancer chemotherapy and improving the therapeutic effect of chemotherapy on breast cancer.

Photosensitive nanosized metal−organic frameworks (nano-MOFs) with a tunable structure and high porosity have been developed recently as nanophotosensitizers (nanoPSs) for photodynamic therapy (PDT). However, the effect of photodynamic therapy is greatly limited by the fast blood clearance and poor tumor retention of the ordinary nanoPSs. Besides, autophagy, a prosurvival self-cannibalization pathway mediated by autolysosomes, was elevated by cytotoxic reactive oxygen species (ROS) produced during PDT. Herein, a chloroquine phosphate (CQ)-loaded photosensitive nanoMOF coated by heparin was fabricated for sensitized PDT by increasing the tumor accumulation of nanoPSs and abolishing the self-protective autophagy within cancer cells. After internalization by cancer cells, the encapsulated CQ alkalizes autolysosomes and blocks the postautophagy process, which disarm the vigilant cancer cells irritated by PDT and finally enhance the therapeutic effect. Furthermore, the accompanied antiangiogenesis ability of the heparin coat also helps improve the cancer therapy outcomes. This study would open up new horizons for building heparin-coated nanoMOFs and understanding the role of autophagy in cancer therapy.

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