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).

Purpose To obtain positive contrast based on T1 weighting from magnetic iron oxide nanoparticle (IONP) using ultrashort echo time (UTE) imaging and investigate quantitative relationship between positive contrast and the core size and concentration of IONPs. Materials and Methods Solutions of IONPs with different core sizes and concentrations were prepared. T1 and T2 relaxation times of IONPs were measured using the inversion recovery turbo spin echo (TSE) and multi-echo spin echo sequences at 3 Tesla. T1-weighted UTE gradient echo and T2-weighted TSE sequences were used to image IONP samples. U87MG glioblastoma cells bound with arginine-glycine-aspartic acid (RGD) peptide and IONP conjugates were scanned using UTE, T1 and T2-weighted sequences. Results Positive contrast was obtained by UTE imaging from IONPs with different core sizes and concentrations. The relative-contrast-to-water ratio of UTE images was three to four times higher than those of T2-weighted TSE images. The signal intensity increases as the function of the core size and concentration. Positive contrast was also evident in cell samples bound with RGD-IONPs. Conclusion UTE imaging allows for imaging of IONPs and IONP bound tumor cells with positive contrast and provides contrast enhancement and potential quantification of IONPs in molecular imaging applications.

We report the application of a versatile diblock copolymer, poly(ethylene oxide)-b-poly(γ-methacryloxypropyl trimethoxysilane) (PEO-b-PγMPS), to prepare nanocrystals such as iron oxide nanoparticles or quantum dots, with either a single core or multi-core cluster, for biomedical applications. This amphiphilic copolymer comprises both a hydrophilic PEO segment and a hydrophobic segment with a "surface anchoring moiety" (the silane group) which can interact effectively with the hydrophobic nanocrystals through ligand exchange. One of the unique features of this work is that we can control the formation of either single core nanoparticles or multi-core nanoclusters by simply varying the conditions of ligand exchange and aging of the mixture of block copolymer and nanoparticles without needing to change the copolymer. The morphologies of the resulting single core nanoparticles or multi-core nanoclusters were confirmed by dynamic light scattering and transmission electron microscopy. The clustered nanoparticles exhibit enhanced physicochemical properties that are beyond those expected from a simple accumulation of individual nanoparticles. Additionally, the hybrid nanoparticles containing both magnetic iron oxide nanoparticles and optical quantum dots obtained using our strategy provide have combined magnetic and optical functionalities that allow for potential new and expanded biomedical applications, as demonstrated by their use for magnetic resonance imaging and biomarker-targeted cell imaging.