Photosensitive Pt(IV)-azide prodrug-loaded nanoparticles exhibit controlled drug release and enhanced efficacy in vivo
文献类型：期刊论文
| 作者 | Xiao, Haihua1; Noble, Gavin T.1; Stefanick, Jared F.1; Qi, Ruogu2,3; Kiziltepe, Tanyel1,4; Jing, Xiabin2; Bilgicer, Basar1,4,5 |
| 刊名 | JOURNAL OF CONTROLLED RELEASE
 |
| 出版日期 | 2014-01-10 |
| 卷号 | 173页码:11-17 |
| 关键词 | Photosensitive Chemotherapy Platinum Drugs Drug Delivery Prodrug Cisplatin Nanomedicine |
| ISSN号 | 0168-3659 |
| DOI | 10.1016/j.jconrel.2013.10.020 |
| 英文摘要 | Cisplatin has long been the first line of treatment for a variety of solid tumors. However, poor pharmacokinetics and high incidences of resistance in the clinic have motivated the production of numerous alternative Pt-based anticancer species. Recently, photosensitive Pt(IV) complexes have garnered much interest because they offer a method of selective induction of active Pt(II) at the tumor site by UVA irradiation. Here, we report the first synthesis, in vitro and in vivo characterization of a novel series of photosensitive Pt(IV)-azide prodrugs and micellar nanoparticle formulations thereof. Upon mild UVA irradiation, both free Pt(IV) complexes and micellar nanoparticles rapidly released biologically active Pt(II), capable of binding to 5'-GMP, while remaining extremely stable in the dark. In vitro, uptake of photosensitive Pt(IV) prodrugs by ovarian cancer SKOV-3 cells was greatly enhanced with the micellar nanoparticles compared to their free prodrug analogs, as well as cisplatin and oxaliplatin. Increased cytotoxicity was observed upon UVA treatment, with up to a 13-fold enhancement over oxaliplatin for the micellar nanoparticles. In vivo bioavailability of micellar nanoparticles was enhanced similar to 10 fold over free Pt(IV) prodrugs. Importantly, micellar nanoparticles demonstrated significantly improved efficacy against H22 murine hepatocarcinoma, showing decreased systemic toxicity and increased tumor growth inhibition relative to small molecule drugs. These findings establish that photosensitive Pt(IV) complexes, specifically when formulated into micellar nanoparticles, have the potential to offer a robust platform for the controlled delivery and selective activation of Pt-based anticancer therapeutics. (C) 2013 Elsevier B.V. All rights reserved. |
| 语种 | 英语 |
| WOS记录号 | WOS:000329157100003 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://ir.iccas.ac.cn/handle/121111/52887]  |
| 专题 | 中国科学院化学研究所 |
| 通讯作者 | Jing, Xiabin |
| 作者单位 | 1.Univ Notre Dame, Dept Chem & Biomol Engn, Notre Dame, IN 46556 USA 2.Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Polymer Phys & Chem, Changchun 130022, Peoples R China 3.Chinese Acad Sci, Grad Sch, Beijing 100049, Peoples R China 4.Univ Notre Dame, Notre Dame, IN 46556 USA 5.Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA |
| 推荐引用方式 GB/T 7714 | Xiao, Haihua,Noble, Gavin T.,Stefanick, Jared F.,et al. Photosensitive Pt(IV)-azide prodrug-loaded nanoparticles exhibit controlled drug release and enhanced efficacy in vivo[J]. JOURNAL OF CONTROLLED RELEASE,2014,173:11-17. |
| APA | Xiao, Haihua.,Noble, Gavin T..,Stefanick, Jared F..,Qi, Ruogu.,Kiziltepe, Tanyel.,...&Bilgicer, Basar.(2014).Photosensitive Pt(IV)-azide prodrug-loaded nanoparticles exhibit controlled drug release and enhanced efficacy in vivo.JOURNAL OF CONTROLLED RELEASE,173,11-17. |
| MLA | Xiao, Haihua,et al."Photosensitive Pt(IV)-azide prodrug-loaded nanoparticles exhibit controlled drug release and enhanced efficacy in vivo".JOURNAL OF CONTROLLED RELEASE 173(2014):11-17. |
入库方式： OAI收割
来源：化学研究所
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