Targeted delivery of antimicrobial peptide by Cry protein crystal to treat intramacrophage infection

Zaofeng Yang, J. Zheng, Chin Fung Chan, Iris L.K. Wong, Bradley S. Heater, Larry M.C. Chow, Marianne M.M. Lee, Michael K. Chan

Research output: Journal article publicationJournal articleAcademic researchpeer-review

5 Citations (Scopus)

Abstract

Antimicrobial peptides (AMPs) have recently attracted great attention due to their rapid action, broad spectrum of activity, and low propensity of resistance development. The successful application of AMPs in the treatment of intracellular infections, however, remains a challenge because of their low penetration efficiency into the pathogen's intracellular niche. Herein, we report that sub-micrometer-sized crystals of the protein Cry3Aa formed within Bacillus thuringiensis are readily and specifically taken up by macrophages. We demonstrate that these protein crystals efficiently encapsulate a known antileishmanial peptide, dermaseptin S1 (DS1), and thereby promote improved cellular uptake of DS1 and its lysosomal accumulation in macrophages. Notably, this targeted delivery of DS1 results in enhanced in vitro and in vivo antileishmanial activity, as well as reduced toxicity to the host macrophages. These findings suggest that the Cry3Aa crystal can be an effective delivery platform for AMPs to treat intramacrophage infections.

Original languageEnglish
Article number119286
JournalBiomaterials
Volume217
DOIs
Publication statusPublished - 1 Oct 2019

Keywords

  • Antimicrobial peptides
  • Cry3Aa protein crystal
  • Intracellular Leishmania
  • Macrophage targeting

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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