Spatial Distribution Control of Antimicrobial Peptides through a Novel Polymeric Carrier for Safe and Efficient Cancer Treatment.

Abstract

Antimicrobial peptides (AMPs) hold great potential for use in tumor treatment. However, developing AMP-based antitumor therapies is challenging due to circulatory instability, hemolytic toxicity, low selectivity, and poor cell permeability of AMPs. In this study, a polymeric carrier for AMPs (denoted as PAMPm -co-PPBEn /PCA) is presented that effectively enhances their anticancer efficacy while minimizing their potential side effects. By integrating multiple responsive structures at the molecular level, the carrier finely controls the spatial distribution of AMPs in different biological microenvironments, thereby effectively modulating their membranolytic ability. Upon employing KLA as the model AMP, the polymeric carrier's hemolytic toxicity during blood circulation is suppressed, its cellular internalization when reaching tumor tissues facilitated, and its membranolytic toxicity toward the mitochondria upon entering cancer cells restored and further enhanced. Animal studies indicate that this approach significantly improves the antitumor efficacy of KLA and reduces its toxicity. Considering that the loading method for most AMPs is identical to that of KLA, the polymeric carrier reported in this study may provide a feasible approach for the development of AMP-based cancer treatments.

• Authors: Ziyao Kang, Chun Wang, Zhanzhan Zhang, Qi Liu, Yadan Zheng, Yu Zhao, Zheng Pan, Qiushi Li, Linqi Shi, Yang Liu
• Journal: Advanced materials (Deerfield Beach, Fla.) (Adv Mater) Vol. 34 Issue 23 Pg. e2201945 (Jun 2022) ISSN: 1521-4095 [Electronic] Germany
• PMID: 35385590 (Publication Type: Journal Article)
• Copyright: © 2022 Wiley-VCH GmbH.

Chemical References

• Antimicrobial Cationic Peptides
• Antimicrobial Peptides
• Polymers

Topics

• Animals
• Antimicrobial Cationic Peptides (pharmacology)
• Antimicrobial Peptides
• Neoplasms (drug therapy)
• Polymers (chemistry)