期刊
JOURNAL OF COLLOID AND INTERFACE SCIENCE
卷 583, 期 -, 页码 672-682出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jcis.2020.09.081
关键词
Antimicrobial peptide delivery; pH-responsive nanocarriers; SAXS; cryo-TEM; Self-assembly; Hierarchically organized particles
资金
- Swiss National Science Foundation [200021_169513]
- National Center of Competence in Research Bio-Inspired Materials
- EU-H2020 research and innovation programme [654360]
- Swiss National Science Foundation (SNF) [200021_169513] Funding Source: Swiss National Science Foundation (SNF)
pH-responsive nanocarriers have the potential to provide targeted delivery of antimicrobial peptides to sites of bacterial infection with abnormal pH levels, and the study demonstrates the tunability of the carriers' pH response range through composition adjustments, advancing our understanding of lipid-peptide self-assembly and pH-responsiveness for future development of adaptable nanocarriers for patient-specific AMP delivery.
Hypothesis: pH-responsive nanocarriers have the potential to provide targeted delivery of antimicrobial peptides (AMPs) to sites of bacterial infection with typically abnormal pH levels in the body. However, the local pH of the infected sites varies substantially among different infection-related diseases, calling for the development of delivery systems capable of targeting local pathological conditions in an adjustable pH range. Experiments: In this study, a highly versatile pH-responsive nanocarrier platform, based on dispersions of oleic acid (OA) and glycerol monooleate (GMO) self-assemblies with the human cathelicidin AMP LL-37, was designed and characterized. Findings: A detailed pH-composition phase diagram was constructed from small angle X-ray scattering and cryogenic transmission electron microscopy data. In addition, the protonation state and apparent pKa of OA embedded in these nano-self-assemblies were investigated by electrophoretic mobility measurements at different pHs and found to be strongly dependent on nanocarrier composition. By varying composition of these nanocarriers, the apparent pK(a) of embedded OA molecules could be tuned from 7.8 to 6.3, shifting the range of nanocarriers' pH-response. The study advances our fundamental understand ing of self-assembly and pH-responsiveness in lipid-peptide systems containing monounsaturated longchain fatty acids. The results may guide the future design of highly adaptable nanocarriers for patientoptimized pH-targeted AMP delivery. (c) 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
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