title: Glioma-Targeted Drug Delivery Enabled by a Multifunctional Peptide.
abstract: The rapid proliferation of glioma relies on vigorous angiogenesis for the supply of essential nutrients; thus, a radical method of antiglioma therapy should include blocking tumor neovasculature formation. A phage display selected heptapeptide, the glioma-initiating cell peptide GICP, was previously reported as a ligand of VAV3 protein (a Rho GTPase guanine nucleotide exchange factor), which is overexpressed on glioma cells and tumor neovasculature. Therefore, GICP holds potential for the multifunctional targeting of glioma (tumor cells and neovasculature). We developed GICP-modified micelle-based paclitaxel delivery systems for antiglioma therapy in vitro and in vivo. GICP and GICP-modified PEG-PLA micelles (GICP-PEG-PLA) could be significantly taken up by U87MG cells, a human cell line derived from malignant gliomas and human umbilical vein endothelial cells (HUVECs). Furthermore, GICP-PEG-PLA micelles demonstrated enhanced penetration in a tumor spheroid model in vitro in comparison to unmodified micelles. In vivo, DiR-loaded GICP-PEG-PLA micelles exhibited superior accumulation in the tumor region by targeting neovasculature and glioma cells in nude mice bearing subcutaneous glioma. When loaded with paclitaxel, GICP-PEG-PLA micelles could more effectively suppress tumor growth and neovasculature formation than unmodified micelles in vivo. Our results indicated that GICP could serve as a promising multifunctional ligand for glioma targeting.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University and Key Laboratory of Smart Drug Delivery , Ministry of Education, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Mingfei
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University and Key Laboratory of Smart Drug Delivery , Ministry of Education, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Xishan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University and Key Laboratory of Smart Drug Delivery , Ministry of Education, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Man
authors.initials: M
authors.lastname: Ying
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University and Key Laboratory of Smart Drug Delivery , Ministry of Education, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.forename: Changyou
authors.initials: C
authors.lastname: Zhan
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University and Key Laboratory of Smart Drug Delivery , Ministry of Education, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Weiyue
authors.identifier: 0000-0001-8003-2675
authors.initials: W
authors.lastname: Lu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000378:metabolism*; D016503:Drug Delivery Systems; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010455:Peptides / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008823:Micelles; D010455:Peptides; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols; D017239:Paclitaxel