Doxorubicin-conjugated chimeric polypeptide nanoparticles that respond to mild hyperthermia

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• 作者：Jonathan R. McDaniel^a ; Sarah R. MacEwan^a ; Mark Dewhirst^a ; ^b ; Ashutosh Chilkoti^a ; ^{chilkoti@duke.edu}
• 关键词：Elastin-like polypeptide ; Hyperthermia ; Targeting ; Nanoparticle ; Thermosensitive ; Cancer
• 刊名：Journal of Controlled Release
• 出版年：2012
• 期刊代码：25_01683659
• 类别：pha
• 出版时间：10 May, 2012
• 卷：159
• 期：3
• 页码：362-367
• 文件大小：511 K

摘要

This paper reports the design, physicochemical characterization and in vitro cytotoxicity of a thermally responsive chimeric polypeptide (CP), derived from an elastin-like polypeptide (ELP). The CP self-assembles into ~ 40 nm diameter nanoparticles upon conjugation of multiple copies of doxorubicin (Dox), and displays a nanoparticle-to-aggregate phase transition between 39 and 42 掳C in media, a temperature range suitable for mild hyperthermia of solid tumors. The CP-Dox nanoparticle is stable upon dilution to low micromolar concentrations, and is cytotoxic at both 37 and 42 掳C. A thermally responsive nanoparticle formulation of Dox may prove to be broadly useful in hyperthermia targeted chemotherapy of a variety of solid tumors.