title: Triple stimulus-responsive polypeptide nanoparticles that enhance intratumoral spatial distribution.
abstract: To address the limited tumor penetration of nanoparticle drug delivery vehicles, we report the first pH-responsive polypeptide micelle that dissociates at the low extracellular pH of solid tumors. This histidine-rich elastin-like polypeptide block copolymer self-assembles at 37 °C into spherical micelles that are stabilized by Zn(2+) and are disrupted as the pH drops from 7.4 to 6.4. These pH-sensitive micelles demonstrate better in vivo penetration and distribution in tumors than a pH-insensitive control.
authors.affiliation: Department of Biomedical Engineering, Duke University, 136 Hudson Hall, Box 90281, Durham, North Carolina 27708, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Callahan
authors.forename: Wenge
authors.initials: W
authors.lastname: Liu
authors.forename: Xinghai
authors.initials: X
authors.lastname: Li
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Dreher
authors.forename: Wafa
authors.initials: W
authors.lastname: Hassouneh
authors.forename: Minkyu
authors.initials: M
authors.lastname: Kim
authors.forename: Piotr
authors.initials: P
authors.lastname: Marszalek
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Chilkoti
mesh_terms: D004337:Drug Carriers / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D006639:Histidine / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000378:metabolism*; D010455:Peptides / Q000032:analysis / Q000378:metabolism*
chemical_list: D004337:Drug Carriers; D008823:Micelles; D010455:Peptides; D006639:Histidine