Reducing non-specific binding and uptake of nanoparticles and improving cell targeting with an antifouling PEO-b-PgammaMPS copolymer coating.

Reducing non-specific binding and uptake of nanoparticles and improving cell targeting with an antifouling PEO-b-PgammaMPS copolymer coating.
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DOI:
10.1016/j.biomaterials.2010.03.036
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发表时间:
2010-07
期刊:
影响因子:
14
通讯作者:
Mao H
Mao H
中科院分区:
工程技术1区
文献类型:
--
作者:
Chen H;Wang L;Yeh J;Wu X;Cao Z;Wang YA;Zhang M;Yang L;Mao H

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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(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).
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