Reducing non-specific binding and uptake of nanoparticles and improving cell targeting with an antifouling PEO-b-PgammaMPS copolymer coating.
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-PgammaMPS), for coating and functionalizing high quality hydrophobic nanocrystals such as iron oxide nanoparticles and quantum dots. These PEO-b-PgammaMPS-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-PgammaMPS 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 heterobifunctional 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.
Chen
Hongwei
H
Department of Radiology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Wang
Liya
L
Yeh
Julie
J
Wu
Xinying
X
Cao
Zehong
Z
Wang
Yongqiang A
YA
Zhang
Minming
M
Yang
Lily
L
Mao
Hui
H
D000818:Animals; D057219:Biofouling / Q000517:prevention & control*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D003470:Culture Media; D006801:Humans; D007501:Iron / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008689:Methacrylates / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D012157:Mononuclear Phagocyte System / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D045663:Quantum Dots; D013050:Spectrometry, Fluorescence; D013194:Staining and Labeling; D014018:Tissue Distribution / Q000187:drug effects
D020099:Coated Materials, Biocompatible; D003470:Culture Media; D008689:Methacrylates; C551302:poly(ethylene oxide)-block-poly(gamma-methacryloxypropyltrimethoxysilane); D011092:Polyethylene Glycols; D007501:Iron
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