title: Internal Structure of 15 nm 3-Helix Micelle Revealed by Small-Angle Neutron Scattering and Coarse-Grained MD Simulation.
abstract: 3-Helix micelles (3HM) formed by self-assembly of peptide-polymer conjugate amphiphiles have shown promise as a nanocarrier platform due to their long-circulation, deep tumor penetration, selective accumulation in tumor, and ability to cross the blood-brain barrier (BBB) for glioblastoma therapy. There is a need to understand the structural contribution to the high in vivo stability and performance of 3HM. Using selective deuteration, the contrast variation technique in small-angle neutron scattering, and coarse-grained molecular dynamics simulation, we determined the spatial distribution of each component within 3HM. Our results show a slightly deformed polyethylene glycol (PEG) conformation within the micelle that is radially offset from its conjugation site toward the exterior of the micelle and a highly solvated shell. Surprisingly, ∼85 v/v % of 3HM is water, unusually higher than any micellar nanocarrier based on our knowledge. The result will provide important structural insights for future studies to uncover the molecular origin of 3HM's in vivo performance, and development of the nanocarriers.
authors: JooChuan
authors: J
authors: Ang
authors: Department of Civil and Environmental Engineering and Department of Mechanical Engineering, Northwestern University , Evanston, Illinois 60208, United States.
authors: Dan
authors: D
authors: Ma
authors: Department of Chemistry, University of Oslo , P.O. Box 1033, Blindern, N-0315 Oslo, Norway.
authors: Reidar
authors: R
authors: Lund
authors: Department of Civil and Environmental Engineering and Department of Mechanical Engineering, Northwestern University , Evanston, Illinois 60208, United States.
authors: Sinan
authors: S
authors: Keten
authors: Material Science Division, Lawrence Berkeley National Laboratory , Berkeley, California 94720, United States.
authors: Ting
authors: T
authors: Xu
mesh_terms: D001812:Blood-Brain Barrier / Q000737:chemistry / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D008823:Micelles; D056004:Molecular Dynamics Simulation; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy; D010455:Peptides / Q000737:chemistry* / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry* / Q000627:therapeutic use; D053838:Scattering, Small Angle; D013501:Surface-Active Agents / Q000737:chemistry* / Q000627:therapeutic use; D014867:Water / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D008823:Micelles; D010455:Peptides; D011108:Polymers; D013501:Surface-Active Agents; D014867:Water; D011092:Polyethylene Glycols