title: Effects of surface displayed targeting ligand GE11 on liposome distribution and extravasation in tumor.
abstract: Targeting ligands displayed on liposome surface had been used to mediate specific interactions and drug delivery to target cells. However, they also affect liposome distribution in vivo, as well as the tissue extravasation processes after IV injection. In this study, we incorporated an EGFR targeting peptide GE11 on liposome surfaces in addition to PEG at different densities and evaluated their targeting properties and antitumor effects. We found that the densities of surface ligand and PEG were critical to target cell binding in vitro as well as pharmacokinetic profiles in vivo. The inclusion of GE11-PEG-DSPE and PEG-DSPE at 2% and 4% mol ratios in the liposome formulation mediated a rapid accumulation of liposomes within 1 h after IV injection in the tumor tissues surrounding neovascular structures. This is in addition to the EPR effect that was most prominently described for surface PEG modified liposomes. Therefore, despite the fact that the distribution of liposomes into interior tumor tissues was still limited by diffusion, GE11 targeted doxorubicin loaded liposomes showed significantly better antitumor activity in tumor bearing mice as a result of the fast active-targeting efficiency. We anticipate these understandings can benefit further optimization of targeted drug delivery systems for improving efficacy in vivo.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University , Shanghai 200240, People's Republic of China.
authors.forename: Hailing
authors.initials: H
authors.lastname: Tang
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Chen
authors.forename: Mengjie
authors.initials: M
authors.lastname: Rui
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Sun
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Jinliang
authors.initials: J
authors.lastname: Peng
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D066246:ErbB Receptors / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry / Q000627:therapeutic use
chemical_list: C572557:GE11 peptide; D008081:Liposomes; D010455:Peptides; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; C541485:EGFR protein, mouse; D066246:ErbB Receptors
keywords: EGFR; GE11; doxorubicin; extravasation; liposome; target delivery