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

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 PEOb-PγMPS coated nanocrystals were colloidally stable in biological medium and showed low nonspecific 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 cocrosslinking the polysiloxane coating layer and (3-Aminopropyl) trimethoxysilane in aqueous solution. Tumor integrin α v β 3 targeting peptide cyclo-RGD ligands were conjugated on the nanoparticles through a heterobifunctional linker. The resulting integrin α v β 3 targeting nanoparticle conjugates showed improved cancer cell targeting with a stronger affinity to U87MG glioma cells, which have a high expression of α v β 3 integrins, but minimal binding to MCF-7 (low expression of α v β 3 integrins).

Magnetic Nanoparticles for Precision Oncology: Theranostic Magnetic Iron Oxide Nanoparticles for Image-Guided and Targeted Cancer Therapy

“…Resulting poly(trimethoxysilyl)propyl methacrylate-PEG-methacrylate-coated SPION had excellent biocompatibility, tumor-targeting ability and long-circulated time in vivo. Additionally, an anti-biofouling polymer-PEO-blockpoly(γ-methacryloxypropyltrimethoxysilane) (PEOb-PγMPS) has been developed to coat IONPs [69]. In comparison with other surface modifications, PEO-b-PγMPS-coated nanoparticles had significantly reduced nonspecific binding to serum proteins and uptake by macrophages in the liver and spleen.…”

Preparation and control of the formation of single core and clustered nanoparticles for biomedical applications using a versatile amphiphilic diblock copolymer

“…Here we demonstrate that when our newly developed polysiloxane-containing amphiphilic diblock copolymer, poly(ethylene oxide)-b-poly(γ-methacryloxypropyl trimethoxysilane) (PEO-b-PγMPS) [20], is employed as a coating for hydrophobic nanocrystals, either single core nanocrystals or multi-core products of the same or different types of nanocrystals (e.g., IONPs and QDs) can be obtained by varying the coating conditions. The versatility and controllability of this block copolymer in forming either single or multi-core nanoparticles is likely due to the hydrophobic PγMPS block.…”

“…PEO-b-PγMPS diblock copolymer was synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization as previously reported [23]. The method for coating single core nanocrystals has been reported elsewhere [20]. For preparing nanoclusters of IONPs and QDs, the fresh mixture of nanocrystals and polymer solution without aging was added dropwise to water.…”

“…Hybrid IONP-QD nanoparticles functionalized with amine groups were conjugated with the thiolated small peptide RGD-SH through a heterobifunctional linker Sulfo-SMCC [20]. For testing the binding of nanoparticles to cancer cells, U87MG human glioma cell line, which over express the tumor integrin α v β 3 , was maintained in a humidified incubator (95% air; 5% CO 2 ) at 37 °C [20].…”

Synthesis, Functionalization, and Design of Magnetic Nanoparticles for Theranostic Applications

“…[338] They were also conjugated with peptides and imaging moieties which consequently showed excellent tumor targeting efficiency, relatively long circulation half-life and limited liver macrophage uptake. Chen et al [339] reported the development of an antibiofouling polysiloxane containing amphiphilic diblock copolymer, poly (ethylene oxide)-block-poly(g-methacryloxypropyl trimethoxysilane) (PEO-b-PgMPS), for coating and functionalizing nanoparticles such as iron oxide and quantum dots. This study demonstrated that PEO-b-PgMPS coated nanoparticles, with nearly neutral surface charge, were colloidally stable in biological medium and showed low non-specific binding by macromolecules after incubation with 100% fetal bovine serum.…”