Development of an anti-microbial peptide-mediated liposomal delivery system: a novel approach towards pH-responsive anti-microbial peptides

Abstract

On one hand, the application of anti-microbial peptides (AMPs) in the construction of AMPs-mediated drug delivery system has not yet been fully exploited; on the other hand, its non-selectivity in vivo has also limited its clinical application. In this work, we chose one pH-responsive peptide, [D]-H₆L₉, and functionalized it onto the surface of liposomes (D-Lip). The protonation of histidines in the sequence of [D]-H₆L₉ under pH 6.3 could switch the surface charge of D-Lip from negative (under pH 7.4) to positive (under pH 6.3), and the cellular uptake and tumor spheroids uptake were increased accordingly. Lysosome co-localization assay suggested that there was only little overlap of D-Lip with lysosomes in 12 h, which indicated that D-Lip could escape lysosomes effectively. In vivo biodistribution assay on C26 tumor-bearing BALB/C mice showed that DiR-labeled D-Lip could reach tumors as much as PEG-Lip, and both tumor slices and quantitative measurement of dispersed cells of in vivo tumors by flow cytometry demonstrated that D-Lip could be taken up by tumors more efficiently. Therefore, we have established an anti-microbial peptide-mediated liposomal delivery system for tumor delivery.

• AMPs
• [D]-H₆L₉ peptide
• liposome
• tumor delivery

Declaration of interest

This work was funded by the National Basic Research Program of China (973 Program, 2013CB932504) and the National Natural Science Foundation of China (81373337).

Supplementary material available online

Supplementary Figure S1.