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

• 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
• Journal Title: Biomaterials
• Volume: Volume 31, Number 20
• Publisher: Elsevier | 2010-07-01, Pages 5397-5407
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.biomaterials.2010.03.036
• Subjects: Biology, Cell; Chemistry, Biochemistry; Health Sciences, Oncology
• Keywords: Nanoparticles; Copolymer; Antifouling; Non-specific binding; Reticuloendothelial system; Cancer targeting

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).