title: [Cellular toxicity and anti-tumor efficacy of iRGD modified doxorubixin loaded sterically stabilized liposomes].
abstract: iRGD-modified sterically stabilized liposomes loaded doxorubicin (iRGD-SSL-DOX) were prepared and their cellular toxicity and anti-tumor efficacy were evaluated, comparing to doxorubixin loaded sterically stabilized liposomes (SSL-DOX) and RGD modified doxorubixin loaded sterically stabilized liposomes (RGD-SSL-DOX). The iRGD peptide, with both tumor targeting and cell penetrating functions, was conjugated to DSPE-PEG-NHS and DSPE-PEG-iRGD was obtained. DSPE-PEG-RGD was gained in the same way. iRGD-SSL-DOX, RGD-SSL-DOX and SSL-DOX were prepared by ammonium sulfate gradient method. The size and zeta potential of the liposomes were characterized by dynamic laser light scattering. The cellular toxicity study was done on B16 melanoma cell line and the anti-tumor efficacy study was carried on B16 cell line bearing C57BL/6 mice. The results showed that the particle sizes of liposomes were all around 90-100 nm. DOX entrapment efficiency was above 95%. The formulations were with good preparation reproducibility. iRGD-SSL-DOX showed no significant difference in B16 cellular toxicity with SSL-DOX and RGD-SSL-DOX, but the anti-tumor efficacy on B16 melanoma bearing C57BL/6 mice was significantly better than that of SSL-DOX, similar as that of RGD-SSL-DOX. Therefore, iRGD modified liposomes loaded DOX would be a promising drug delivery system for tumor therapy.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhao
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Fan
authors.forename: Xue-Qing
authors.initials: XQ
authors.lastname: Wang
authors.forename: Wen-Bing
authors.initials: WB
authors.lastname: Dai
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xing-Lin
authors.initials: XL
authors.lastname: Wang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D008081:Liposomes; D008297:Male; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D047368:Tumor Burden / Q000187:drug effects
chemical_list: C512968:1,2-dioleoyl-3-phosphoethanolamine-n-(poly(ethyleneglycol))-hydroxy succinamide; D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; C569656:N-end cysteine peptide tumor-homing peptide; D009842:Oligopeptides; D010714:Phosphatidylethanolamines; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D004317:Doxorubicin