Reducing Non-Specific Binding and Uptake of Nanoparticles and Improving Cell Targeting with an Antifouling PEO-b-PγMPS Copolymer Coating

• Type of Material: Article
• Authors: Hongwei Chen, Emory University; Liya Wang, Emory University; Julie Yeh, Emory University; Xinying Wu, Emory University; Zehong Cao, Emory University; Ya Wang, Emory University; Minming Zhang, Zhejiang University; Lily Yang, Emory University; Hui Mao, Emory University
• Language: English
• Date: 2010-07-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 Elsevier Ltd. Published by Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.biomaterials.2010.03.036
• Title of Journal or Parent Work: Biomaterials
• ISSN: 0142-9612
• Volume: 31
• Issue: 20
• Start Page: 5397
• End Page: 5407
• Grant/Funding Information: This work in part is supported by the Emory-Georgia Tech Nanotechnology Center for Personalized and Predictive Oncology of NIH NCI Center of Cancer Nanotechnology Excellence (CCNE, U54 CA119338-01 to HM and LY), Emory Molecular Translational Imaging Center of NIH in vivo Cellular and Molecular Imaging Center grant (ICMIC, P50CA128301-01A10003 to HM and LY), and a research grant from EmTech Bio, Inc.
• Keywords: Cancer targeting; Antifouling; Non-specific binding; Reticuloendothelial system; Nanoparticles; Copolymer
• Research Categories: Chemistry, Biochemistry; Health Sciences, Oncology; Biology, Cell

Abstract

One of the major limitations impeding the sensitivity and specificity of biomarker targeted nanoparticles is non-specific binding by biomolecules and uptake by the reticuloendothelial system (RES). We report the development of an antibiofouling polysiloxane containing amphiphilic diblock copolymer, poly(ethylene oxide)-block-poly(γ-methacryloxypropyltrimethoxysilane) (PEO-b-PγMPS), for coating and functionalizing high quality hydrophobic nanocrystals such as iron oxide nanoparticles and quantum dots. These PEO-b-PγMPS coated nanocrystals were colloidally stable in biological medium and showed low non-specific binding by macromolecules after incubation with 100% fetal bovine serum. Both in vitro experiments with macrophages and in vivo biodistribution studies in mice revealed that PEO-b-PγMPS copolymer coated nanocrystals have an antibiofouling effect that reduces non-specific cell and RES uptake. Surface functionalization with amine groups was accomplished through co-crosslinking the polysiloxane coating layer and (3-Aminopropyl) trimethoxysilane in aqueous solution. Tumor integrin αvβ3 targeting peptide cyclo-RGD ligands were conjugated on the nanoparticles through a heterobifunctional linker. The resulting integrin αvβ3 targeting nanoparticle conjugates showed improved cancer cell targeting with a stronger affinity to U87MG glioma cells, which have a high expression of αvβ3 integrins, but minimal binding to MCF-7 (low expression of αvβ3 integrins).