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.
Centre for Advanced Macromolecular Design (CAMD), School of Chemical Sciences and Engineering, The University of New South Wales (UNSW), Sydney, NSW 2052, Australia.
Zhongfan
Z
Jia
Jingquan
J
Liu
Cyrille
C
Boyer
Thomas P
TP
Davis
Volga
V
Bulmus
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