Targeted delivery of antimicrobial peptide by Cry protein crystal to treat intramacrophage infection
| Autor: | Marianne M. Lee, Iris L. K. Wong, Jiale Zheng, Zaofeng Yang, Larry M.C. Chow, Bradley S. Heater, Michael K. Chan, Chin-Fung Chan |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Antimicrobial peptides
Biophysics Bioengineering Peptide 02 engineering and technology Hemolysis Amphibian Proteins Microbiology Biomaterials Hemolysin Proteins Inhibitory Concentration 50 03 medical and health sciences Drug Delivery Systems Bacterial Proteins In vivo Cell Line Tumor Animals Humans Pathogen 030304 developmental biology Leishmania chemistry.chemical_classification Mice Inbred BALB C 0303 health sciences Dermaseptin Bacillus thuringiensis Toxins Chemistry 021001 nanoscience & nanotechnology Antimicrobial In vitro Endotoxins Mechanics of Materials Macrophages Peritoneal Ceramics and Composites Female Lysosomes 0210 nano-technology Intracellular Antimicrobial Cationic Peptides |
| Zdroj: | Biomaterials. 217:119286 |
| ISSN: | 0142-9612 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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