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

作者：Zhang, Qianyu; Lu, Libao; Zhang, Li; Shi, Kairong; Cun, Xingli; Yang, Yuting; Liu, Yayuan; Gao, Huile; He, Qin^*

来源：Scientific Reports, 2016, 6(1): 19800.

DOI：10.1038/srep19800

• CELL-PENETRATING PEPTIDE
• TARGETED DRUG-DELIVERY
• ALPHA(V)BETA(3) INTEGRIN
• POLYMERIC MICELLES
• CANCER
• LIGAND
• NANOPARTICLES
• DOXORUBICIN
• PACLITAXEL
• EFFICACY

[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 alpha(v)beta(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 alpha(v)beta(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 alpha(v)beta(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.

• 出版日期2016-2-4
• 单位四川大学