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 it number of reasons. First, they possess free biotin binding sites oil their streptavidin (SAv) coated surface, enabling the conjugation of any biotinylated-molecule such as biotinylated antibodies. Second, core-stabilization call easily be controlled using reversible disulfide cross-links, and third, thiol- and ene-reactive functionalities in the core ate 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-pol y(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 % ability), as determined by a streptavidin/HABA assay. The micelles were subsequently decorated with (red avail, fluorophore-labeled) streptavidin (SAv) through the accessible biotins on the surface, yielding SM-linked micelle aggregates with tunable dimensions (in the range between 350 rim and 2 pin), as determined by transmission electron microscopy. Fluorescent-labels oil the particles were monitored using confocal microscopy, revealing that the SAv coats the periphery of the PPHPs.