Biodistribution and Clearance of Stable Superparamagnetic Maghemite Iron Oxide Nanoparticles in Mice Following Intraperitoneal Administration.

Nanomedicine is an emerging field with great potential in disease theranostics. We generated sterically stabilized superparamagnetic iron oxide nanoparticles (s-SPIONs) with average core diameters of 10 and 25 nm and determined the in vivo biodistribution and clearance profiles. Healthy nude mice underwent an intraperitoneal injection of these s-SPIONs at a dose of 90 mg Fe/kg body weight. Tissue iron biodistribution was monitored by atomic absorption spectroscopy and Prussian blue staining. Histopathological examination was performed to assess tissue toxicity. The 10 nm s-SPIONs resulted in higher tissue-iron levels, whereas the 25 nm s-SPIONs peaked earlier and cleared faster. Increased iron levels were detected in all organs and body fluids tested except for the brain, with notable increases in the liver, spleen, and the omentum. The tissue-iron returned to control or near control levels within 7 days post-injection, except in the omentum, which had the largest and most variable accumulation of s-SPIONs. No obvious tissue changes were noted although an influx of macrophages was observed in several tissues suggesting their involvement in s-SPION sequestration and clearance. These results demonstrate that the s-SPIONs do not degrade or aggregate in vivo and intraperitoneal administration is well tolerated, with a broad and transient biodistribution. In an ovarian tumor model, s-SPIONs were shown to accumulate in the tumors, highlighting their potential use as a chemotherapy delivery agent.

Room temperature, aqueous post-polymerization modification of glycidyl methacrylate-containing polymer brushes prepared via surface-initiated atom transfer radical polymerization.

This manuscript reports on the post-polymerization modification of poly(glycidyl methacrylate) (PGMA) and PGMA-co-poly(2-(diethylamino)ethyl methacrylate) (PGMA(x)-co-PDEAEMA(y)) (co)polymer brushes prepared via surface-initiated atom transfer radical polymerization (SI-ATRP). The aim of this study was to evaluate the ability of tertiary amine groups incorporated in the polymer brush to accelerate the ring-opening of the epoxide groups by primary amines and to facilitate the aqueous, room temperature post-polymerization modification of the brushes. Using Fourier transform infrared (FTIR) spectroscopy to monitor the ring-opening reaction of the epoxide groups, it was found that the incorporation of 2-(diethylamino)ethyl methacrylate (DEAEMA) groups in the PGMA brushes significantly accelerated the rate of the post-polymerization modification reaction with several model amines. The rate enhancement was dependent on the fraction of DEAEMA units incorporated in the copolymer brush. For example, whereas 24 h was necessary to obtain a conversion of approximately 40% for PGMA brushes immersed in a 1 M propylamine solution in water, the same conversion was reached, in identical reaction conditions, after 8 and 2 h with copolymer brushes containing 10 mol % and 25 mol % of DEAEMA along the copolymer chains, respectively. In a final series of proof-of-concept experiments, the feasibility of the glycidyl methacrylate containing brushes to act as substrates for protein immobilization was studied. Using FTIR spectroscopy and quartz crystal microbalance with dissipation (QCM-D) experiments, it could be demonstrated that the incorporation of DEAEMA units not only enhanced the rate of the protein immobilization reaction, but also resulted in higher protein binding capacities as compared to a PGMA homopolymer brush. These features make PGMA(x)-co-PDEAEMA(y) brushes very attractive candidates for the development of protein microarrays, among others.

Protein microarrays based on polymer brushes prepared via surface-initiated atom transfer radical polymerization.

Polymer brushes represent an interesting platform for the development of high-capacity protein binding surfaces. Whereas the protein binding properties of polymer brushes have been investigated before, this manuscript evaluates the feasibility of poly(glycidyl methacrylate) (PGMA) and PGMA-co-poly(2-(diethylamino)ethyl methacrylate) (PGMA-co-PDEAEMA) (co)polymer brushes grown via surface-initiated atom transfer radical polymerization (SI-ATRP) as protein reactive substrates in a commercially available microarray system using tantalum-pentoxide-coated optical waveguide-based chips. The performance of the polymer-brush-based protein microarray chips is assessed using commercially available dodecylphosphate (DDP)-modified chips as the benchmark. In contrast to the 2D planar, DDP-coated chips, the polymer-brush-covered chips represent a 3D sampling volume. This was reflected in the results of protein immobilization studies, which indicated that the polymer-brush-based coatings had a higher protein binding capacity as compared to the reference substrates. The protein binding capacity of the polymer-brush-based coatings was found to increase with increasing brush thickness and could also be enhanced by copolymerization of 2-(diethylamino)ethyl methacrylate (DEAEMA), which catalyzes epoxide ring-opening of the glycidyl methacrylate (GMA) units. The performance of the polymer-brush-based microarray chips was evaluated in two proof-of-concept microarray experiments, which involved the detection of biotin-streptavidin binding as well as a model TNFα reverse assay. These experiments revealed that the use of polymer-brush-modified microarray chips resulted not only in the highest absolute fluorescence readouts, reflecting the 3D nature and enhanced sampling volume provided by the brush coating, but also in significantly enhanced signal-to-noise ratios. These characteristics make the proposed polymer brushes an attractive alternative to commercially available, 2D microarray surface coatings.

A Facile Route to Functional Hyperbranched Polymers by Combining Reversible Addition-Fragmentation Chain Transfer Polymerization, Thiol-Yne Chemistry, and Postpolymerization Modification Strategies.

This contribution reports on the preparation of functional hyperbranched polystyrene-based materials via a combination of reversible addition-fragmentation chain transfer (RAFT) polymerization, thiol-yne chemistry, and postpolymerization modification reactions. The thiol-yne approach allows the rapid preparation of hyperbranched polymers under mild reaction conditions from polymeric chains bearing a thiol group at one chain end and an alkyne moiety at the other. Postpolymerization modifications of the focal thiol and peripheral alkyne functionalities present within the hyperbranched structures were conducted using two highly efficient strategies, i.e., phosphine-catalyzed thiol-ene reaction and copper-catalyzed azide-alkyne cycloaddition (CuAAC), respectively. In addition to introducing functionalities by postpolymerization modification onto the periphery of the hyperbranched polymers, the interior of the globular structure could also be functionalized by taking advantage of the isocyanate chemical handle of a poly(styrene-co-3-isopropenyl-α,α-dimethylbenzyl isocyanate) (P(S-co-TMI)) copolymer. The combination of these strategies provides an elegant tool for the elaboration of a wide variety of multifunctional hyperbranched structures.

Nonfouling Polypeptide Brushes via Surface-initiated Polymerization of N(ε) -oligo(ethylene glycol)succinate-L-lysine N-carboxyanhydride.

This contribution describes the preparation of nonfouling polypeptide brushes via surface-initiated ring-opening polymerization of oligo(ethylene glycol) modified L-lysine N-carboxyanhydrides. Circular dichroism experiments indicated that these surface-anchored polypeptide chains assume an α-helical conformation, which does not change between pH 4 and 9. Furthermore, nonspecific adsorption of fluorescent labeled bovine serum albumin and fibrinogen on glass slides modified with these brushes was greatly reduced compared to unmodified glass substrates.