Heparin-Coated
Photosensitive Metal–Organic
Frameworks as Drug Delivery Nanoplatforms of Autophagy Inhibitors
for Sensitized Photodynamic Therapy against Breast Cancer
posted on 2021-11-11, 18:36authored byQuanwei Sun, Xiaohui Hou, Jinming Yang, Mengmeng Zhang, Ye Yang, Yang Liu, Wei Shen, Dengke Yin
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.