title: NGR-modified micelles enhance their interaction with CD13-overexpressing tumor and endothelial cells.
abstract: Certain tumor cells and most tumor endothelial cells overexpress a membrane-spanning molecule, aminopeptidase N (CD13) isoform, which is the receptor for peptides containing the Asn-Gly-Arg (NGR) motif. NGR-modified docetaxel (DTX)-loaded PEG-b-PLA polymeric micelles (NGR-PM-DTX) were firstly developed and tested in vitro and in vivo, while DTX-loaded polymeric micelles (PM-DTX) and free DTX were used as controls. The NGR-PM-DTX containing DTX were about 35 nm in diameter with spherical shape and high encapsulation efficiency. It was demonstrated quantitatively by the spectrophotofluorometry and qualitatively by the confocal image analysis that NGR facilitates the uptake of micelles by CD13-overexpressed tumor cells (fibrosarcoma, HT1080) and endothelial cells (human umbilical vein endothelial cells, HUVEC). Free NGR inhibited cellular uptake of NGR-PM-DTX, revealing the mechanism of receptor-mediated endocytosis. Higher cytotoxicity toward HT1080 cells and more efficient inhibition of HUVEC proliferation were also observed in NGR-PM-DTX groups, which were consistent well with the observation of cellular uptake. In BALB/c mice bearing HT1080 tumor xenografts, stronger antitumor efficacy and less body weight changes were shown in NGR-PM-DTX group, with good correlation between in vitro and in vivo. Therefore, it was concluded that NGR-PM could be a potential vehicle for delivering hydrophobic chemotherapeutic agents to CD13-overexpressing tumors.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People's Republic of China.
authors.forename: Xun
authors.initials: X
authors.lastname: Wang
authors.forename: Yiguang
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Chen
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Wang
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology; D018826:CD13 Antigens / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D000077143:Docetaxel; D004339:Drug Compounding; D004355:Drug Stability; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D018613:Microscopy, Confocal; D009842:Oligopeptides / Q000737:chemistry*; D010316:Particle Size; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology; D013696:Temperature; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; C526428:NGR peptide; D009842:Oligopeptides; D043823:Taxoids; D000077143:Docetaxel; D018826:CD13 Antigens