Dual-functionalized liposomal delivery system for solid tumors based on RGD and a pH-responsive antimicrobial peptide.

ABSTRACT: [D]-H6L9, as a pH-responsive anti-microbial peptide (AMP), has been evidenced by us to be an excellent choice in tumor microenvironment-responsive delivery as it could render liposomes responsive to the acidified tumor microenvironment. However, [D]-H6L9-modified liposomes could not actively target to tumor area. Therefore, integrin ?v?3-targeted peptide RGD was co-modified with [D]-H6L9 onto liposomes [(R?+?D)-Lip] for improved tumor delivery efficiency. Under pH 6.3, (R?+?D)-Lip could be taken up by C26 cells and C26 tumor spheroids (integrin ?v?3-positive) with significantly improved efficiency compared with other groups, which was contributed by both RGD and [D]-H6L9, while RGD did not increase the cellular uptake performance on MCF-7 cells (integrin ?v?3-negative). Results showed that RGD could decrease cellular uptake of (R?+?D)-Lip while [D]-H6L9 could increase it, implying the role of both RGD and [D]-H6L9 in cellular internalization of (R?+?D)-Lip. On the other hand, (R?+?D)-Lip could escape the entrapment of lysosomes. PTX-loaded (R?+?D)-Lip could further increase the cellular toxicity against C26 cells compared with liposomes modified only with RGD and [D]-H6L9 respectively, and achieve remarkable tumor inhibition effect on C26 tumor models.

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC4740748 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature