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.
Highlights
Anti-microbial peptides (AMPs), termed as host-defense peptides, as the names suggests, are a class of peptides that possess direct anti-microbial activities (Zasloff, 2002; Reddy et al, 2004; Di Francesco, 2013)
Substituting all the lysines in the peptide sequence into histidines ([D]-H6L9), a well-known amino acid with an imidazole ring and protonation effect, could accord pH-responsiveness to the peptide and reduce its non-selective penetration under pH 7.4, decreasing systemic cytotoxicity (Makovitzki et al, 2009). This methodology has been widely employed in designing peptides with pH-dependent activity, be it anti-microbial peptides (AMPs) or cell penetrating peptide (CPP) (Tu et al, 2009; Zhang et al, 2011; Chen et al, 2012; Jiang et al, 2012; Tian & Bae, 2012; Zhao et al, 2012), as solid tumors were notable for their high acidity due to low oxygen tension and anaerobic glycolysis (Tannock & Rotin, 1989; Hancock & Sahl, 2006)
When the amount of DSPEPEG2000-[D]-H6L9 increased to 8%, the turbidity started to decline below 90% from 4 h to 24 h, which was probably due to the excessive presence of [D]-H6L9 that was detrimental to the serum stability of liposomes, and this required further verification in the future
Summary
Anti-microbial peptides (AMPs), termed as host-defense peptides, as the names suggests, are a class of peptides that possess direct anti-microbial activities (Zasloff, 2002; Reddy et al, 2004; Di Francesco, 2013). Substituting all the lysines in the peptide sequence into histidines ([D]-H6L9), a well-known amino acid with an imidazole ring and protonation effect, could accord pH-responsiveness to the peptide and reduce its non-selective penetration under pH 7.4, decreasing systemic cytotoxicity (Makovitzki et al, 2009) This methodology has been widely employed in designing peptides with pH-dependent activity, be it AMP or cell penetrating peptide (CPP) (Tu et al, 2009; Zhang et al, 2011; Chen et al, 2012; Jiang et al, 2012; Tian & Bae, 2012; Zhao et al, 2012), as solid tumors were notable for their high acidity due to low oxygen tension and anaerobic glycolysis (Tannock & Rotin, 1989; Hancock & Sahl, 2006)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
