title: Specific tumor delivery of paclitaxel using glycolipid-like polymer micelles containing gold nanospheres.
abstract: It is difficult for most of the drug delivery systems to really display a temporal and spatial release of entrapped drug once the systems are iv administrated. We hypothesized that the photothermal effect, mediated by a near-infrared (NIR) laser and hollow gold nanospheres (HAuNS), can modulate paclitaxel (PTX) release from polymer micelles, and further result in the enhanced antitumor activity of the micelles. We loaded PTX and HAuNS, which display strong plasmon absorption in the NIR region, into glycolipid-like polymer micelles with an excellent cell internalization capability. The surface of the micelles was conjugated successfully with a peptide, which has the specific-binding with EphB4, a member of the Eph family of receptor tyrosine kinases overexpressed on cell membrane of numerous tumors, to increase the delivery of PTX into tumor cells. Rapid and repetitive drug release from our polymer (HP-TCS) micelles could be readily achieved upon NIR laser irradiation. Our data demonstrated the specific delivery of HP-TCS micelles into positive-EphB4 tumors using a duel-tumor model after iv administration during the whole experiment process (1-48 h). Interestingly, significantly higher uptake of the micelles by SKOV3 tumors (positive-EphB4) than A549 tumors (negtive-EphB4) was observed, with increased ratio on experiment time. However, the specific cell uptake was observed only during the short incubation time (1-4 h) in vitro. Our data also indicated the treatment of tumor cells with the micelles followed by NIR laser irradiation showed significantly greater toxicity activity than the treatment with the micelles alone, free PTX and the micelles (without PTX loading) plus NIR laser irradiation. The enhanced toxicity activity to tumor cells should be attributed to the enhanced drug cellular uptake mediated by the glycolipid-like micelles, chemical toxicity of the released drug from the micelles due to the trigger of NIR laser, and the photothermal ablation under NIR laser irradiation.
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China. youjiandoc@zju.edu.cn
authors.forename: Jian
authors.initials: J
authors.lastname: You
authors.forename: Zuhua
authors.initials: Z
authors.lastname: Wang
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: Du
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.forename: Peizun
authors.initials: P
authors.lastname: Zhang
authors.forename: Jialin
authors.initials: J
authors.lastname: Zhou
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Hu
mesh_terms: D055011:Ablation Techniques; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry; D003952:Diagnostic Imaging; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D006017:Glycolipids / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D006801:Humans; D008027:Light; D051379:Mice; D008823:Micelles; D054118:Nanospheres / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009844:Oligosaccharides / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010316:Particle Size; D010455:Peptides / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D036224:Receptor, EphB4; D019265:Spectroscopy, Near-Infrared; D055672:Static Electricity; D013229:Stearic Acids / Q000737:chemistry; D013696:Temperature
chemical_list: D006017:Glycolipids; D008823:Micelles; D009844:Oligosaccharides; D010455:Peptides; D011108:Polymers; D013229:Stearic Acids; C031183:stearic acid; D006046:Gold; D048271:Chitosan; D036224:Receptor, EphB4; D017239:Paclitaxel