Doxorubicin-conjugated chimeric polypeptide nanoparticles that respond to mild hyperthermia

作者：McDaniel Jonathan R; MacEwan Sarah R; Dewhirst Mark; Chilkoti Ashutosh^*

来源：Journal of Controlled Release, 2012, 159(3): 362-367.

DOI：10.1016/j.jconrel.2012.02.030

• Elastin-like polypeptide
• Hyperthermia
• Targeting
• Nanoparticle
• Thermosensitive
• Cancer

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 similar to 40 nm diameter nanoparticles upon conjugation of multiple copies of doxorubicin (Dox), and displays a nanoparticle-to-aggregate phase transition between 39 and 42 degrees 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 degrees C. A thermally responsive nanoparticle formulation of Dox may prove to be broadly useful in hyperthermia targeted chemotherapy of a variety of solid tumors.

• 出版日期2012-5-10