Tumor microenvironment (TME)-activatable circular aptamer-PEG as an effective hierarchical-targeting molecular medicine for photodynamic therapy
2020
Yang, Yu | Zhu, Wenjun | Cheng, Liang | Cai, Ren | Yi, Xuan | He, Jiaxuan | Pan, Xiaoshu | Yang, Lu | Yang, Kai | Liu, Zhuang | Tan, Weihong | Chen, Meiwan
Photodynamic therapy (PDT) is an effective and noninvasive therapeutic strategy employing light-triggered singlet oxygen (SO) and reactive oxygen species (ROS) to kill lesional cells. However, for effective in vivo delivery of PDT agent into the cancer cells, various biological obstacles including blood circulation and condense extracellular matrix (ECM) in the tumor microenvironment (TME) need to be overcome. Furthermore, the enormous challenge in design of smart drug delivery systems is meeting the difference, even contradictory required functions, in different steps of the complicated delivery process. To this end, we present that TME-activatable circular pyrochlorophyll A (PA)-aptamer-PEG (PA-Apt–CHO–PEG) nanostructures, which combine the advantages of PEG and aptamer, would be able to realize efficient in vivo imaging and PDT. Upon intravenous (i.v.) injection, PA-Apt–CHO–PEG shows “stealth-like” long circulation in blood compartments without specific recognition capacity, but once inside solid tumor, PA-Apt–CHO–PEG nanostructures are cleaved and then form PA-Apt Aptamer-drug conjugations (ApDCs) in situ, allowing deep penetration into the solid tumor and specific recognition of cancer cells, both merits, considering anticipated future clinical translation of ApDCs.
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