Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 13, Issue 46, Pages 55577-55590Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c18055
Keywords
metal-organic framework; heparin; autophagy inhibition; sensitized photodynamic therapy; breast cancer
Funding
- National Science Foundation Plan of Anhui Province [201904b11020023]
- Natural Science Foundation of Anhui Province [1908085J29]
- academic funding for top talents in disciplines (Specialties) of Anhui Provincial Higher Education Institutes [gxbjZD2021056]
- Exploratory Fund of Anhui University of Chinese Medicine [2021zxt31]
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Photosensitive nanosized metal-organic frameworks have been developed as nanophotosensitizers for photodynamic therapy, but their effectiveness is limited by fast blood clearance and poor tumor retention. Researchers fabricated a CQ-loaded photosensitive nanoMOF coated with heparin to sensitize PDT, increasing the tumor accumulation of nanoPSs and eliminating self-protective autophagy in cancer cells.
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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