Determination of the Bioavailability of Biotin Conjugated onto Shell Cross-Linked (SCK) Nanoparticles

Abstract

Shell cross-linked nanoparticles (SCKs) presenting surface- and bioavailable biotin functional groups were synthesized via a mixed micelle methodology, whereby co-micellization of chain terminal biotinylated poly(acrylic acid)-b-poly(methyl acrylate) (PAA-b-PMA) and nonbiotinylated PAA-b-PMA were cross-linked in an intramicellar fashion within the shell layer of the mixed micelles, between the carboxylic acid groups of PAA and the amine functionalities of 2,2'-(ethylenedioxy)diethylamine. The hydrodynamic diameters (D(h)) of the micelles and the SCKs with different biotinylated block copolymer contents were determined by dynamic light scattering (DLS), and the dimensions of the SCKs were characterized with tapping-mode atomic force microscopy (AFM) and transmission electron microscopy (TEM). The amount of surface-available biotin was tuned by varying the stoichiometric ratio of the biotinylated PAA-b-PMA versus the nonbiotinylated PAA-b-PMA, as demonstrated with solution-state, binding interaction analyses, an avidin/HABA (avidin/4'-hydroxyazobenzene-2-carboxylic acid) competitive binding assay, and fluorescence correlation spectroscopy (FCS). The avidin/HABA assay found the amount of available biotin at the surface of the biotinylated SCK nanoparticles to increase with increasing biotin-terminated block copolymer incorporation, but to be less than 25% of the theoretical value. FCS measurements showed the same trend.

PEGylated polymers for medicine: from conjugation to self-assembled systems

“…Examples of micelles with cross-links in the corona are referred to as shell cross-linked micelles (SCMs), or shell cross-linked nanoparticles (termed SCKs, after the initially-coined term ''shell cross-linked knedels''). Wooley and co-workers described the preparation and characterization of SCKs in 1996, 141 and the concept has since been extended considerably to provide a suite of tailored nanoparticles for drug delivery, 142 by the addition of biologically active moieties, [143][144][145][146][147] imaging agents, 148,149 stimuli-sensitive and degradable linkages, 11,13,150,151 core excavation, 16 and PEGylation. 152 One recent detailed study compared PEGylated and non-PEGylated SCK's with different hydrophobic cores, one consisting of the malleable poly(methyl acrylate), and the other composed of hard polystyrene.…”

Tandem Chain Walking Polymerization and Atom Transfer Radical Polymerization for Efficient Synthesis of Dendritic Nanoparticles for Bioconjugation

“…The molecular weight and molecular size data for the core-shell copolymers increase with the ATRP polymerization time. (Table 1, entry [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Again, consistent with the dendritic coreshell topology, the relative molecular weight values obtained by regular SEC are much smaller than the absolute values measured by MALS.…”

“…1 In parallel to the development of inorganic nanoparticles for these applications, organic nanostructures have received increasing attention recently because in principle organic synthesis can provide more precise control over molecular structure, size and functionality of nanostructures. [2][3][4][5] Among others, nanoparticles based on dendritic macromolecules are especially attractive because they have globular shape in solution with molecular dimensions right in the nanometer range. 6,7 However, the difficulty of preparing dendrimers through step-wise synthesis and the ultimate size limit for regular dendrimers warrant the search of more efficient methodologies for constructing dendritic nanoparticles.…”

Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors

“…A shell cross-linked micelle (SCM) has been previously reported and was achieved via radical oligomerization of the pendent styrenyl groups on the coronal blocks in a tetrahydrofuran-water mixture. [13][14][15] Structure and drug encapsulation of the SCM were more stable than noncrosslinked micelle (NCM) with respect to infinite dilution in the blood circulation. Nevertheless, the drugs loaded into the SCM could not quickly release in cells; it had to follow a passive diffusion because of the nonsensitive cores of the SCM.…”