Rational Design of Self-Assembled Mitochondria-Targeting Lytic Peptide Conjugates with Enhanced Tumor Selectivity |
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Authors: | Sijin Liu Biao Wang Yina Sheng Dr Suwei Dong Dr Guoquan Liu |
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Institution: | 1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China;2. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China
These authors contributed equally to this work. |
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Abstract: | 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. |
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Keywords: | lysosomal escape membrane lytic peptides mitochondria-targeting self-assembly tumor selectivity |
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