[Preparation of doxorubicin-loaded stealth liposomes modified with RGD mimetic and cellular association in vitro].
OBJECTIVE
To 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.


METHODS
RGD 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.


RESULTS
The 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.


CONCLUSIONS
The 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.
School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
Xiao-bing
XB
Xiong
Yue
Y
Huang
Wan-liang
WL
Lü
Xuan
X
Zhang
Hua
H
Zhang
Qiang
Q
Zhang
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage* / Q000378:metabolism; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D008081:Liposomes; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology*; D009842:Oligopeptides; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D009842:Oligopeptides; D010714:Phosphatidylethanolamines; C038089:1,2-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; D004317:Doxorubicin