Tumor-Triggered Disassembly of a Multiple-Agent-Therapy Probe for Efficient Cellular Internalization

作者：Yang, Juliang; Dai, Jun; Wang, Quan; Cheng, Yong; Guo, Jingjing; Zhao, Zujin; Hong, Yuning; Lou, Xiaoding^*; Xia, Fan

来源：Angewandte Chemie - International Edition, 2020, 59(46): 20405-20410.

DOI：10.1002/anie.202009196

• caveolae-mediated endocytosis
• macropinocytosis
• multiple-agent-therapy probes
• nanofibers
• gene
• ROS
• peptide-conjugated-AIEgens

Integration of multiple agent therapy (MAT) into one probe is promising for improving therapeutic efficiency for cancer treatment. However, MAT probe, if entering the cell as a whole, may not be optimal for each therapeutic agent (with different physicochemical properties), to achieve their best performance, hindering strategy optimization. A peptide-conjugated-AIEgen (FC-PyTPA) is presented: upon loading with siRNA, it self-assembles into FCsiRNA-PyTPA. When approaching the region near tumor cells, FCsiRNA-PyTPA responds to extracellular MMP-2 and is cleaved into FC(siRNA)and PyTPA. The former enters cells mainly by macropinocytosis and the latter is internalized into cells mainly through caveolae-mediated endocytosis. This two-part strategy greatly improves the internalization efficiency of each individual therapeutic agent. Inside the cell, self-assembly of nanofiber precursor F, gene interference of C-siRNA, and ROS production of PyTPA are activated to inhibit tumor growth.

• 单位
  华中科技大学