title: Rational design of "heat seeking" drug loaded polypeptide nanoparticles that thermally target solid tumors.
abstract: This paper demonstrates the first example of targeting a solid tumor that is externally heated to 42 °C by "heat seeking" drug-loaded polypeptide nanoparticles. These nanoparticles consist of a thermally responsive elastin-like polypeptide (ELP) conjugated to multiple copies of a hydrophobic cancer drug. To rationally design drug-loaded nanoparticles that exhibit thermal responsiveness in the narrow temperature range between 37 and 42 °C, an analytical model was developed that relates ELP composition and chain length to the nanoparticle phase transition temperature. Suitable candidates were designed based on the predictions of the model and tested in vivo by intravital confocal fluorescence microscopy of solid tumors, which revealed that the nanoparticles aggregate in the vasculature of tumors heated to 42 °C and that the aggregation is reversible as the temperature reverts to 37 °C. Biodistribution studies showed that the most effective strategy to target the nanoparticles to tumors is to thermally cycle the tumors between 37 and 42 °C. These nanoparticles set the stage for the targeted delivery of a range of cancer chemotherapeutics by externally applied mild hyperthermia of solid tumors.
authors.affiliation: Department of Biomedical Engineering, Duke University , Durham, North Carolina 27708-0281, United States.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: McDaniel
authors.forename: Sarah R
authors.initials: SR
authors.lastname: MacEwan
authors.forename: Xinghai
authors.initials: X
authors.lastname: Li
authors.forename: D Christopher
authors.initials: DC
authors.lastname: Radford
authors.forename: Chelsea D
authors.initials: CD
authors.lastname: Landon
authors.forename: Mark
authors.initials: M
authors.lastname: Dewhirst
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Chilkoti
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy*; D016503:Drug Delivery Systems; D004549:Elastin / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D006979:Hyperthermia, Induced; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D010455:Peptides; D004549:Elastin
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