Functional disulfide-stabilized polymer-protein particles.
Polymer-protein hybrid particles (PPHPs) have a significant potential in drug delivery, diagnosis, and biomedical imaging applications. Herein, we describe a simple route to disulfide cross-linked, poly(ethylene glycol)-streptavidin hybrid particles with tunable diameters. These particles have great versatility and potential for a number of reasons. First, they possess free biotin binding sites on their streptavidin (SAv) coated surface, enabling the conjugation of any biotinylated-molecule such as biotinylated antibodies. Second, core-stabilization can easily be controlled using reversible disulfide cross-links, and third, thiol- and ene-reactive functionalities in the core are available for the conjugation of drugs and labels. In detail, micelles having a biotinylated poly(ethylene glycol) corona and a disulfide cross-linked, reactive core were formed using alpha-biotin PEG-b-poly(pyridyldisulfide ethylmethacrylate) block copolymers synthesized via RAFT polymerization. Functionalization of the micelle core was performed in a one-pot reaction concurrent with the micellization and cross-linking processes by using a thiol-reactive model compound (a maleimide derivative of a green fluorophore). The resultant micelles displayed spherical morphology with a diameter of 54 +/- 4 nm. Biotin functionality was largely exposed on the micelle corona (75 mol % availability), as determined by a streptavidin/HABA assay. The micelles were subsequently decorated with (red fluorophore-labeled) streptavidin (SAv) through the accessible biotins on the surface, yielding SAv-linked micelle aggregates with tunable dimensions (in the range between 350 nm and 2 microm), as determined by transmission electron microscopy. Fluorescent-labels on the particles were monitored using confocal microscopy, revealing that the SAv coats the periphery of the PPHPs.
Jia
Zhongfan
Z
Centre for Advanced Macromolecular Design (CAMD), School of Chemical Sciences and Engineering, The University of New South Wales (UNSW), Sydney, NSW 2052, Australia.
Liu
Jingquan
J
Boyer
Cyrille
C
Davis
Thomas P
TP
Bulmus
Volga
V
D004220:Disulfides / Q000737:chemistry*; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D019809:Streptavidin / Q000737:chemistry*
D004220:Disulfides; D008823:Micelles; D011109:Polymethacrylic Acids; C546911:alpha-biotin polyethylene glycol-b-poly(pyridyldisulfide ethylmethacrylate); D011092:Polyethylene Glycols; D019809:Streptavidin