Journal
BIOMATERIALS
Volume 31, Issue 20, Pages 5397-5407Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2010.03.036
Keywords
Nanoparticles; Copolymer; Antifouling; Non-specific binding; Reticuloendothelial system; Cancer targeting
Funding
- Emory-Georgia Tech Nanotechnology Center for Personalized and Predictive Oncology of NIH NCI Center of Cancer Nanotechnology Excellence (CCNE) [U54 CA119338-01]
- Emory Molecular Translational Imaging Center of NIH [P50CA128301-01A10003]
- EmTech Bio, Inc
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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(gamma-methacryloxypropyl trimethoxysilane) (PEO-b-P gamma MPS), for coating and functionalizing high quality hydrophobic nanocrystals such as iron oxide nanoparticles and quantum dots. These PEO-b-P gamma MPS-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-P gamma MPS 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 alpha(v)beta(3) targeting peptide cyclo-RGD ligands were conjugated on the nanoparticles through a hetero-bifunctional linker. The resulting integrin alpha(v)beta(3) targeting nanoparticle conjugates showed improved cancer cell targeting with a stronger affinity to U87MG glioma cells, which have a high expression of alpha(v)beta(3) integrins, but minimal binding to MCF-7 breast cancer cells with low expression of alpha(v)beta(3) integrins. (C) 2010 Elsevier Ltd. All rights reserved.
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