Photosensitive Chitosan-Based Injectable Hydrogel Chemically Cross-Linked by Perylene Bisimide Dopamine with Robust Antioxidant and Cytotoxicity Enhancer Properties for In Vitro Photodynamic Therapy of Breast Cancer.

Abstract

Here, we report the fabrication of an antioxidant photosensitizing hydrogel system based on chitosan (CS-Cy/PBI-DOPA) covalently cross-linked with perylene bisimide dopamine (PBI-DOPA) as a photosensitizer. The severe insolubility and low tumor selectivity limitations of perylene were overcome by conjugation with dopamine and then to the chitosan hydrogel. The mechanical and rheological study of CS-Cy/PBI-DOPA photodynamic antioxidant hydrogels illustrated interconnected microporous morphologies with high elasticity, swelling ability, and suitable shear-thinning behavior. Bio-friendly properties, such as biodegradability and biocompatibility, excellent singlet oxygen production abilities, and antioxidant properties were also delivered. The antioxidant effects of the hydrogels control the physiological levels of reactive oxygen species (ROS) generated by photochemical reactions in photodynamic therapy (PDT), which are responsible for oxidative damage to tumor cells while protecting normal cells and tissues from ROS damage, including blood and endothelial cells. In vitro, PDT tests of hydrogels were conducted on two human breast cancer cell lines, MDA-MB-231 and MCF-7. These hydrogels offered more than 90% cell viability in the dark and good photocytotoxicity performance with 53 and 43% cell death for MCF-7 and MDA-MB-231 cells, which confirmed their promising potential for cancer therapeutic applications.