Carrier-Enhanced Photodynamic Cancer Therapy of Self-Assembled Green Tea Polyphenol-Based Nanoformulations

Abstract

Recently, various nanotechnologies have been developed to improve the current photodynamic cancer therapy, which is generally associated with the deficiencies of photosensitizers including poor solubility, inadequate photodynamic activity, and high dark toxicity. Naturally resourced green tea polyphenols, especially (−)-epigallocatechin-3-gallate (EGCG), are well documented to have intrinsic antitumor activity. In this work, the self-assembly of EGCG-conjugated poly(ethylene glycol) (PEG) (EGP) and chlorin e6 (Ce6) was conducted to fabricate polyphenol nanoparticles (EGP–Ce6 NPs) for achieving carrier-enhanced photodynamic cancer therapy. Among different groups of EGP–Ce6 NPs with the ratio of EGCG to Ce6 varying from 0.5, 1.0 to 2.0, EGP–Ce6/0.5 NPs had the maximum drug loading (44%) and encapsulation rate (89%). The self-assembled EGP–Ce6 NPs had good solubility and minimal dark toxicity. Compared with free drugs, EGP–Ce6 NPs showed enhanced effects in intracellular uptake, reactive oxygen species (ROS) generation, and penetrability into multicellular tumor spheres, indicative of their feasibility as photodynamic agents. Furthermore, EGP–Ce6 NPs were verified to integrate the photodynamic effect of the photosensitizer Ce6 with the antitumor effect of EGP, realizing the carrier-enhanced photodynamic cancer therapy. This study proposed a simple strategy by utilizing green tea polyphenol-based nanotechnology to resolve the shortcomings of photosensitizers along with enhanced antitumor efficiency, spearheading the application of natural products in photodynamic therapies for not only carcinoma but also dermatologic, infectious, and cardiovascular diseases.