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2294039 
Journal Article 
Improvement of pharmacokinetic and antitumor activity of PEGylated liposomal doxorubicin by targeting with N-methylated cyclic RGD peptide in mice bearing C-26 colon carcinomas 
Amin, M; Badiee, A; Jaafari, MR 
2013 
Yes 
International Journal of Pharmaceutics
ISSN: 0378-5173
EISSN: 1873-3476 
458 
2 
324-333 
English 
24148663 
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.