Carrier Free Photodynamic Synergists for Oxidative Damage Amplified Tumor Therapy

作者：Xinyu Li, Fu‐An Deng, Rongrong Zheng, Lingshan Liu, Yibin Liu, Renjiang Kong, Ali Chen, Xiyong Yu, Shiying Li, Hong Cheng · 发表于：Small · 年份：2021 · DOI：10.1002/smll.202102470 · 被引用次数：68 · 研究领域：Nanoplatforms for cancer theranostics、Photodynamic Therapy Research Studies、Luminescence and Fluorescent Materials

Tumor cells adapt to excessive oxidative stress by actuating reactive oxygen species (ROS)-defensing system, leading to a resistance to oxidation therapy. In this work, self-delivery photodynamic synergists (designated as PhotoSyn) are developed for oxidative damage amplified tumor therapy. Specifically, PhotoSyn are fabricated by the self-assembly of chlorine e6 (Ce6) and TH588 through π-π stacking and hydrophobic interactions. Without additional carriers, nanoscale PhotoSyn possess an extremely high drug loading rate (up to 100%) and they are found to be fairly stable in aqueous phase with a uniform size distribution. Intravenously injected PhotoSyn prefer to accumulate at tumor sites for effective cellular uptake. More importantly, TH588-mediated MTH1 inhibition could destroy the ROS-defensing system of tumor cells by preventing the elimination of 8-oxo-2'-deoxyguanosine triphosphate (8-oxo-dG), thereby exacerbating the oxidative DNA damage induced by the photodynamic therapy (PDT) of Ce6 under light irradiation. As a consequence, PhotoSyn exhibit enhanced photo toxicity and a significant antitumor effect. This amplified oxidative damage strategy improves the PDT efficiency with a reduced side effect by increasing the lethality of ROS without generating superabundant ROS, which would provide a new insight for developing self-delivery nanoplatforms in photodynamic tumor therapy in clinic.