Carrier Free Photodynamic Synergists for Oxidative Damage Amplified Tumor Therapy

作者：Li, Xin-Yu; Deng, Fu-An; Zheng, Rong-Rong; Liu, Ling-Shan; Liu, Yi-Bin; Kong, Ren-Jiang; Chen, A-Li; Yu, Xi-Yong; Li, Shi-Ying^*; Cheng, Hong^*

来源：Small, 2021, 17(40): 2102470.

DOI：10.1002/smll.202102470

• MTH1 inhibition
• nanoplatform
• oxidative damage
• photodynamic therapy
• self-delivery

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 pi-pi 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.

• 单位
  广州医学院; 南方医科大学