4.8 Article

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

Journal

ADVANCED MATERIALS
Volume 34, Issue 23, Pages -

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202201945

Keywords

antimicrobial peptides; cancer treatment; membranolytic toxicity; polymeric carriers; spatial distribution control

Funding

  1. National Key Research and Development Programs of China [2018YFA0209700]
  2. National Natural Science Foundation of China (NSFC) [22077073]
  3. Frontiers Science Center for New Organic Matter, Nankai University [63181206]
  4. Fundamental Research Funds for the Central Universities, Nankai University [63206015]

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The study presents a polymeric carrier for antimicrobial peptides that enhances their anticancer efficacy while reducing potential side effects.
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 PAMP(m)-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.

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