Article ID Journal Published Year Pages File Type
2502040 International Journal of Pharmaceutics 2013 10 Pages PDF
Abstract

Cyclic Arg-Gly-Asp (cRGD) pentapeptides engrafted liposomes have attracted considerable attention for targeting integrin receptors on tumor vasculature. In this study PEGylated liposomal doxorubicin (PLD) was decorated with three cRGD peptides including Arg-Gly-Asp-D-Tyr-Cys (RGDyC), Arg-Gly-Asp-D-Phe-Lys (RGDfK) and Arg-Gly-Asp-D-Phe-[N-Methyl]Lys (RGDf[N-Met]K). The in vitro liposome-cell-association and cytotoxicity experiments demonstrated the RGD-PLDs capability of internalization into integrin expressing HUVEC cells via receptor mediated endocytosis. The biodistribution studies revealed that decreasing the hydrophilicity of the peptide greatly reduces the RGD-PLDs blood clearance rate and increases their localization in C-26 colon carcinoma tumor model. Meanwhile, the most selective version, RGDf[N-Met]K, which has intermediate hydrophilicity revealed the lowest unwanted interactions with other integrin presenting sites, further localization in tumor, and lower doxorubicin (Dox) side effects. RGDf[N-Met]K-PLD demonstrated a superior control of tumor growth and increased the survival of mice. In this study, we introduced RGDf[N-Met]K for the first time, as a promising ligand for active targeting of liposomes to solid tumor which merits further investigations.

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