Amphiphilic block copolymers bearing ortho ester side-chains: pH-dependent hydrolysis and self-assembly in water.
A new type of pH-responsive block copolymer nanoparticle has been synthesized and characterized. The amphiphilic diblock copolymer, PEG-b-PMYM, contains acid-labile ortho ester side-chains in the hydrophobic block and can self-assemble into micelle-like nanoparticles in water at neutral pH. Hydrolysis of the ortho ester side-chains follows a distinct exocyclic mechanism and shows pH-dependent kinetics, which triggers changes in nanoparticle size and morphology. The nanoparticles have been found to be non-toxic to cells in vitro. The ability to tune the size and morphology of biocompatible block copolymer nanoparticles by controlling the pH-sensitive side-chain hydrolysis represents a unique approach that may be exploited to improve the efficacy of nanometer-scale drug delivery.
Tang
Rupei
R
Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Ji
Weihang
W
Wang
Chun
C
D000178:Acrylamides / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D016503:Drug Delivery Systems; D004952:Esters / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D006868:Hydrolysis / Q000187:drug effects; D007700:Kinetics; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008970:Molecular Weight; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000633:toxicity / Q000648:ultrastructure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry / Q000633:toxicity; D011108:Polymers / Q000737:chemistry* / Q000633:toxicity; D012542:Scattering, Radiation; D013050:Spectrometry, Fluorescence; D013997:Time Factors; D014867:Water / Q000737:chemistry*
D000178:Acrylamides; D004952:Esters; D011108:Polymers; D014867:Water; D011092:Polyethylene Glycols; C045985:methacrylamide