title: Doxorubicin-conjugated chimeric polypeptide nanoparticles that respond to mild hyperthermia.
abstract: 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 °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 °C. A thermally responsive nanoparticle formulation of Dox may prove to be broadly useful in hyperthermia targeted chemotherapy of a variety of solid tumors.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC 27708-0281, USA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: McDaniel
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Macewan
authors.forename: Mark
authors.initials: M
authors.lastname: Dewhirst
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Chilkoti
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D015195:Drug Design; D004591:Electrophoresis, Polyacrylamide Gel; D006358:Hot Temperature; D051379:Mice; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry* / Q000235:genetics; D019151:Peptide Library; D044367:Phase Transition; D013499:Surface Properties; D044366:Transition Temperature
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D009842:Oligopeptides; D019151:Peptide Library; D004317:Doxorubicin