Synthetic lipo-polylysine with anti-cancer activity

Development of novel therapeutic agents that possess different anticancer mechanisms from the traditional antitumor drugs is highly attractive as no medication can cure all types of cancers. Herein, we report a rational design of antitumor lipo-polylysine polymers as synthetic mimics of biosynthetic lipopeptide surfactants featuring antimicrobial or cytotoxic activities for cancer therapy. The optimal polymer shows a wide range of anticancer activities against multiple cancer cells, including highly metastatic and drug-resistant ones, but low toxicity to normal cells. Mechanism studies show that the optimal polymer can interact with the membrane of cancer cells and induce cell necrosis by triggering cell membrane perforation, which is different from the therapeutic mechanisms of traditional anticancer drugs. In vivo studies imply that the optimal polymer efficiently inhibits tumor growth without causing obvious side effects on a C26 graft tumor model. Overall, the lipopeptide-mimicking lipo-polylysine with the advantages of easy synthesis and low cost provides a new anticancer strategy with high efficacy and biocompatibility.

Automated summary

This study reports the design and synthesis of antitumor lipo-polylysine polymers as synthetic mimics of biosynthetic lipopeptide surfactants for cancer therapy. The optimal polymer exhibits broad-spectrum anticancer activity against multiple cancer cells, including drug-resistant ones, while showing low toxicity to normal cells. Mechanistically, the optimal polymer interacts with the cancer cell membrane and induces necrosis by perforating the cell membrane, which is different from the mechanism of traditional anticancer drugs. In vivo studies demonstrate that the optimal polymer efficiently inhibits tumor growth without causing obvious side effects. Overall, the lipopeptide-mimicking lipo-polylysine provides a new, cost-effective, and biocompatible anticancer strategy with high efficacy.