title: Tumor-penetrating peptide functionalization enhances the anti-glioblastoma effect of doxorubicin liposomes.
abstract: The targeted therapeutic effect of nano drug delivery system for glioblastoma has been hampered by the weak enhanced permeability and retention (EPR) effect of glioblastoma and the low delivering efficiency of NDDS in glioblastoma tissue. In this study, a tumor-penetrating peptide (RGERPPR), the specific ligand of neuropilin-1 overexpressed on glioblastoma and endothelial cells, was used as a targeting moiety to enhance the anti-glioblastoma effect of doxorubicin liposomes. Firstly, RGERPPR-PEG-DSPE was synthesized and used to prepare the RGERPPR peptide-functionalized liposomes (RGE-LS), which showed vesicle sizes of around 90 nm and narrow size distributions. The cellular uptake and in vivo near-infrared fluorescence imaging test displayed that RGE-LS exhibited increased uptake by glioblastoma cells and intracranial glioblastoma tissues. The cytotoxicity assay and anti-glioblastoma study proved that RGERPPR functionalization significantly enhanced the in vitro inhibitory effect of doxorubicin liposomes on glioblastoma cells and prolonged the median survival time of nude mice bearing intracranial glioblastoma. Finally, the immunofluorescence analysis evidenced that RGE-LS were able to penetrate through tumor vessels and stroma and deep into the whole tumor tissue. The results indicated that tumor-penetrating peptide functionalization is an effective strategy for enhancing the anti-glioblastoma effect of doxorubicin liposomes.
authors.affiliation: School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China. National Engineering Research Center for Nanotechnology, Shanghai 200241, People's Republic of China.
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Yang
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yan
authors.forename: Daixu
authors.initials: D
authors.lastname: Wei
authors.forename: Jian
authors.initials: J
authors.lastname: Zhong
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wei
authors.forename: Cao
authors.initials: C
authors.lastname: Xie
authors.forename: Weiyue
authors.initials: W
authors.lastname: Lu
authors.forename: Dannong
authors.initials: D
authors.lastname: He
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality; D053208:Kaplan-Meier Estimate; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D010455:Peptides; D004317:Doxorubicin