RGD-based strategies for improving antitumor activity of paclitaxel-loaded liposomes in nude mice xenografted with human ovarian cancer

Abstract

Tumor-targeting drug delivery systems are being the ideal carrier for systemic administration of antiproliferative drugs. RGD peptide (arginine–glycine–aspartic acid) modified liposomes containing paclitaxel (RGD-SSL-PTX). The arginine-glycine-aspartic acid tripeptide (RGD) modified sterically stabilized liposomes (SSL) containing paclitaxel (PTX) (RGD-SSL-PTX), which could increase targeting to tumor by binding with the integrin receptors overexpressed on tumor cells. The encapsulation efficiency was more than 90% and the mean particle size was of 120 nm with a narrow size distribution. It was indicated that significant cytotoxicity (3.5 times lower IC₅₀) was found in the SKOV-3 human ovarian cancer cells treated with RGD-SSL-PTX preparation, as well as the intracellular uptake of liposomes (a 6.21-fold increase in fluorescence intensity), when compared to those of non-targeted liposomes (SSL). For in vivo antitumor activity, it was shown in the present study that RGD-SSL-PTX preparation had the strongest tumor growth inhibition among the test formulations (P < 0.05) in BALB/c nude mice xenografted with SKOV-3 solid tumor. Meanwhile, there was no significant change in the body weight of the animals treated with RGD-SSL-PTX for intravenous injection at a dose of 12.5 mg/kg. It was suggested that the RGD-SSL-PTX preparation might have a great advantage over present-day chemotherapy with Taxol^® in curing those tumors overexpressing integrin receptors.

Keywords::

• RGD peptide
• targeting liposomes
• paclitaxel
• antitumor

Acknowledgements

We wish to thank Sun Shufeng, Chunchun Liu, LanLan Yuan, and Wenyan Hao for their valuable assistance on this research. This work was supported by the grants from the National Natural Science Foundation of China (Grant nos. 30430760 and 30572261) and the National Basic Research Program of China (973 program, no. 2007CB935801).

Declaration of interest: The authors report no conflicts of interest.