at Peking University School of Pharmaceutical Sciences
​​​​the dong research group
18. Rational Design of Self-Assembled Mitochondria-Targeting Lytic Peptide Conjugates with Enhanced Tumor Selectivity
Chem. Eur. J. 2022, 28, e202103517.
Sijin Liu, Biao Wang, Yina Sheng, Dr. Suwei Dong* ,Dr. Guoquan Liu*

Membrane lytic peptides (MLP) are widely explored as cellular delivery vehicles or antitumor/antibacterial agents. However, the poor selectivity between cancer and normal cells slims their prospects as potential anti-tumor drugs. Herein, we have developed a rationally designed self-assembly strategy to enhance tumor selectivity of MLP-based conjugates, incorporating a hydrophobic triphenylphosphonium (TPP) group for mitochondria targeting, and a hydrophilic arginine-glycine-aspartic acid (RGD) sequence targeting integrins. The self-assembly nanoparticles can enhance the stability of the peptides in vitro plasma and be endocytosed selectively into the cancer cells. The histidine-rich lytic peptide component assists the disruption of endosomal/lysosomal membranes and subsequent the mitochondria membrane, which leads to apoptosis. This rational design of MLP-based conjugates provides a practical strategy to increase the application prospects of lytic peptides in cancer treatment.