Preparation of doxorubicin-loaded stealth liposomes modified with RGD mimetic and cellular association in vitro.
- Author:
Xiao-bing XIONG
1
;
Yue HUANG
;
Wan-liang LÜ
;
Xuan ZHANG
;
Hua ZHANG
;
Qiang ZHANG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Antibiotics, Antineoplastic; administration & dosage; metabolism; Cell Adhesion; Cell Line, Tumor; Cell Nucleus; metabolism; Doxorubicin; administration & dosage; metabolism; Drug Carriers; Drug Delivery Systems; Humans; Liposomes; Melanoma, Experimental; metabolism; pathology; Oligopeptides; Phosphatidylethanolamines; Polyethylene Glycols
- From: Acta Pharmaceutica Sinica 2005;40(12):1085-1090
- CountryChina
- Language:Chinese
-
Abstract:
AIMTo investigate the possibility of using stealth liposomes modified with arginine-glycine-aspartic acid (RGD) mimetic as the targeted carriers to achieve increased accumulation in tumor and enhanced intracellular delivery for the encapsulated anticancer drugs.
METHODSRGD mimetic (RGDm) as a ligand for integrins was synthesized and covalently conjugated to the active PEGylated phospholipids (DSPE-PEG-BTC) to form RGDm conjugate (DSPE-PEG-RGDm). Then RGDm-modified SL (RGDm-SL) containing DOX (RGDm-SL-DOX) and SL containing DOX (SL-DOX) were prepared by film dispersion followed by ammonium sulfate gradient method. The pH-sensitive probe, BCECF-AM, was used to study the binding of melanoma cells to DSPE-PEG-RGDm. Flow cytometry and confocal microscopy were performed to evaluate the cellular association or DOX uptake for RGDm-SL-DOX or SL-DOX in vitro.
RESULTSThe melanoma cells A375 and B16 showed enhanced binding to the immobilized DSPE-PEG-RGDm. The cells treated with RGDm-SL-DOX showed remarkable increase in cellular association or DOX uptake compared with SL-DOX.
CONCLUSIONThe RGDm-modified SL could be as the targeted carriers to facilitate the delivery of the encapsulated anti-cancer drugs into tumor cells by receptor-mediated way.
