title: Controlled apoptosis by a thermally toggled nanoscale amplifier of cellular uptake.
abstract: Internalization into cancer cells is a significant challenge in the delivery of many anticancer therapeutics. Drug carriers can address this challenge by facilitating cellular uptake of cytotoxic cargo in the tumor, while preventing cellular uptake in healthy tissues. Here we describe an extrinsically controlled drug carrier, a nanopeptifier, that amplifies cellular uptake by modulating the activity of cell-penetrating peptides with thermally toggled self-assembly of a genetically encoded polypeptide nanoparticle. When appended with a proapoptotic peptide, the nanopeptifier creates a cytotoxic switch, inducing apoptosis only in its self-assembled state. The nanopeptifier provides a new approach to tune the cellular uptake and activity of anticancer therapeutics by an extrinsic thermal trigger.
authors.affiliation: Department of Biomedical Engineering and ‡Research Triangle MRSEC, Duke University , Durham, North Carolina 27708, United States.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: MacEwan
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Chilkoti
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D057846:Cell-Penetrating Peptides; D003692:Delayed-Action Preparations; D010455:Peptides