Heparin-Coated Photosensitive Metal-Organic Frameworks as Drug Delivery Nanoplatforms of Autophagy Inhibitors for Sensitized Photodynamic Therapy against Breast Cancer

Photosensitive nanosized metal-organic frameworks (nanoMOFs) 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.