title: Multifunctional surface modification of gold-stabilized nanoparticles by bioorthogonal reactions.
abstract: Nanocarriers that combine multiple properties in an all-in-one system hold great promise for drug delivery. The absence of technology to assemble highly functionalized devices has, however, hindered progress in nanomedicine. To address this deficiency, we have chemically synthesized poly(ethylene oxide)-β-poly(ε-caprolactone) (PEO-b-PCL) block polymers modified at the apolar PCL terminus with thioctic acid and at the polar PEO terminus with an acylhydrazide, amine, or azide moiety. The resulting block polymers were employed to prepare nanoparticles that have a gold core, an apolar polyester layer for drug loading, a polar PEO corona to provide biocompatibility, and three different types of surface reactive groups for surface functionalization. The acylhydrazide, amine, or azide moieties of the resulting nanoparticles could be reacted with high efficiencies with modules having a ketone, isocyanate, or active ester and alkyne function, respectively. To demonstrate proof of principle of the potential of multisurface functionalization, we prepared nanoparticles that have various combinations of an oligo-arginine peptide to facilitate cellular uptake, a histidine-rich peptide to escape from lysosomes, and an Alexa Fluor 488 tag for imaging purposes. It has been shown that uptake and subcellular localization of the nanoparticles can be controlled by multisurface modification. It is to be expected that the modular synthetic methodology provides unique opportunities to establish optimal configurations of nanocarriers for disease-specific drug delivery.
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia 315 Riverbend Road, Athens, Georgia 30602, USA.
authors.forename: Xiuru
authors.initials: X
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.forename: Jinkeng
authors.initials: J
authors.lastname: Asong
authors.forename: Margreet A
authors.initials: MA
authors.lastname: Wolfert
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: Boons
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D006046:Gold / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D007783:Lactones / Q000737:chemistry; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000737:chemistry; D013499:Surface Properties; D008063:Thioctic Acid / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D007783:Lactones; C473831:poly(ethylene oxide)-b-poly(caprolactone); D011092:Polyethylene Glycols; D008063:Thioctic Acid; D006046:Gold