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Author Notes:

Correspondence: Hui Mao, PhD, Department of Radiology, Center for Systems Imaging, Emory University School of Medicine, 1364 Clifton Road, Atlanta, GA 30322; Phone: (404) 712-0357; Fax: (404) 712-5948; Email: hmao@emory.edu

Subjects:

Research Funding:

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:

  • Nanoparticles
  • Copolymer
  • Antifouling
  • Non-specific binding
  • Reticuloendothelial system
  • Cancer targeting

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

Tools:

Journal Title:

Biomaterials

Volume:

Volume 31, Number 20

Publisher:

, Pages 5397-5407

Type of Work:

Article | Post-print: After Peer Review

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).

Copyright information:

© 2010 Elsevier Ltd. Published by Elsevier Ltd. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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