Branched α-helical peptides enhanced antitumor efficacy and selectivity.

Biomater Sci

Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310020, PR China.

Published: November 2020

AI Article Synopsis

  • Drug resistance to traditional cancer treatments is a major challenge, prompting researchers to explore cationic antimicrobial peptides (CAPs) as potential anticancer agents.
  • A specific 4-arm branched peptide {[(LLKK)2]2κC}2 demonstrated superior effectiveness and selectivity against drug-resistant cancer cells compared to linear and 2-arm branched peptides.
  • In animal studies, this branched peptide showed the ability to reduce tumor growth while having low toxicity to vital organs, highlighting its potential as a promising anticancer therapy.

Article Abstract

Drug resistance to traditional chemotherapeutics is one of the main challenges in cancer treatment. Herein, cationic antimicrobial peptides (CAPs) were repurposed as anticancer agents to counter chemotherapy drug resistance. After a systematic study of de novo designed synthetic α-helical CAPs in various cell lines, the 4-arm branched peptide {[(LLKK)2]2κC}2 was found to exhibit better selectivity compared to its linear counterpart (LLKK)4, and was more effective than the 2-arm branched peptide [(LLKK)2]2κC. In particular, the 4-arm branched peptide could counter drug resistance and kill multiple drug resistant cells. Mechanism studies reveal that these α-helical peptides killed both the parent and resistant cancer cells based on the apoptotic pathway. The in vivo study in mice bearing breast tumors showed that branched peptides could be retained at the tumour sites after intratumoral injection and significantly reduced tumor growth while exhibiting minimal toxicity on main organs. These results indicate that the 4-arm branched peptide is a promising candidate for anticancer therapy.

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Source
http://dx.doi.org/10.1039/d0bm00629gDOI Listing

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