Etoposide-Bound Magnetic Nanoparticles Designed for Remote Targeting of Cancer Cells Disseminated Within Cerebrospinal Fluid Pathways.

Magnetic nanoparticles (MNPs) have potential for enhancing drug delivery in selected cancer patients, including those which have cells that have disseminated within cerebrospinal fluid (CSF) pathways. Here, we present data related to the creation and in vitro use of new two-part MNPs consisting of magnetic gold-iron alloy cores which have streptavidin binding sites, and are coated with biotinylated etoposide. Etoposide was chosen due to its previous use in the CSF and ease of biotinylation. Etoposide magnetic nanoparticles ("Etop-MNPs") were characterized by several different methods, and moved at a distance by surface-walking of MNP clusters, which occurs in response to a rotating permanent magnet. Human cell lines including D283 (medulloblastoma), U138 (glioblastoma), and H2122 (lung adenocarcinoma) were treated with direct application of Etop-MNPs (and control particles), and after remote particle movement. Cell viability was determined by MTT assay and trypan blue exclusion. Results indicated that the biotinylated etoposide was successfully bound to the base MNPs, with the hybrid particle attaining a maximum velocity of 0.13 ± 0.018 cm/sec. Etop-MNPs killed cancer cells in a dose-dependent fashion, with 50 ± 6.8% cell killing of D283 cells (for example) with 24 h of treatment after remote targeting. U138 and H2122 cells were found to be even more susceptible to the killing effect of Etop-MNPs than D283 cells. These findings indicate that the novel Etop-MNPs have a cytotoxic effect, and can be moved relatively rapidly at physiologic distances, using a rotating magnet. While further testing is needed, intrathecal administration of Etop-MNPs holds promise for magnetically-enhanced eradication of cancer cells distributed within CSF pathways, particularly if given early in the course of the disease.

Self-Assembled Au@Fe Core/Satellite Magnetic Nanoparticles for Versatile Biomolecule Functionalization.

Although the functionalization of magnetic nanoparticles (MNPs) with biomolecules has been widely explored for various biological applications, achieving efficient bioconjugations with a wide range of biomolecules through a single, universal, and versatile platform remains a challenge, which may significantly impact their applications' outcomes. Here, we report a novel MNP platform composed of Au@Fe core/satellite nanoparticles (CSNPs) for versatile and efficient bioconjugations. The engineering of the CSNPs is facilely formed through the self-assembly of ultrasmall gold nanoparticles (AuNPs, 2-3 nm in diameter) around MNPs with a polysiloxane-containing polymer coating. The formation of the hybrid magnetic nanostructure is revealed by absorption spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), element analysis using atomic absorption spectroscopy, and vibrating sample magnetometer. The versatility of biomolecule loading to the CSNP is revealed through the bioconjugation of a wide range of relevant biomolecules, including streptavidin, antibodies, peptides, and oligonucleotides. Characterizations including DLS, TEM, lateral flow strip assay, fluorescence assay, giant magnetoresistive nanosensor array, high-performance liquid chromatography, and absorption spectrum are performed to further confirm the efficiency of various bioconjugations to the CSNP. In conclusion, this study demonstrates that the CSNP is a novel MNP-based platform that offers versatile and efficient surface functionalization with various biomolecules.

Spatioselective growth of metal-organic framework nanocrystals on compositionally anisotropic polymer particles.

Selective growth of metal organic framework materials on the surface of compartmentalized polymer microparticles is achieved by electro-hydrodynamic co-jetting, selective surface modification, and anisotropic crystal growth.

Photoswitchable particles for on-demand degradation and triggered release.

On-demand degradable polymer particles are fabricated via electrospraying of a solution of acetal-protected dextran that further includes 2-(4-methoxystyryl)-4,6-bis(trichloromethyl)-1,3,5-triazine as a photoacid generator. The illumination of UV light gives rise to photoacid and activates the catalytic deprotection of hydroxyl groups of dextran, leading to controlled dissolution of the microparticles in water.

Janus-core and shell microfibers.

Janus microcylinders composed of different polymers were prepared through coaxial co-jetting with dual-core flows, followed by cross-linking, microsectioning, and shell removal. Uniquely shaped building blocks can be fabricated by photo-patterning of one hemisphere of the microcylinders.

Spontaneous shape reconfigurations in multicompartmental microcylinders.

Nature's particles, such as spores, viruses or cells, are adaptive--i.e., they can rapidly alter major phenomenological attributes such as shape, size, or curvature in response to environmental changes. Prominent examples include the hydration-mediated opening of ice plant seeds, actuation of pine cones, or the ingenious snapping mechanism of predatory Venus flytraps that rely on concave-to-convex reconfigurations. In contrast, experimental realization of reconfigurable synthetic microparticles has been extremely challenging and only very few examples have been reported so far. Here, we demonstrate a generic approach towards dynamically reconfigurable microparticles that explores unique anisotropic particle architectures, rather than direct synthesis of sophisticated materials such as shape-memory polymers. Solely enabled by their architecture, multicompartmental microcylinders made of conventional polymers underwent active reconfiguration including shape-shifting, reversible switching, or three-way toggling. Once microcylinders with appropriate multicompartmental architectures were prepared by electrohydrodynamic cojetting, simple exposure to an external stimulus, such as ultrasound or an appropriate solvent, gives rise to interfacial stresses that ultimately cause reversible topographical reconfiguration. The broad versatility of the electrohydrodynamic cojetting process with respect to materials selection and processing suggests strategies for a wide range of dynamically reconfigurable adaptive materials including those with prospective applications for sensors, reprogrammable microactuators, or targeted drug delivery.

Differentially degradable janus particles for controlled release applications.

Janus particles with differentially degradable compartments were prepared by electrohydrodynamic (EHD) co-jetting and subsequent controlled crosslinking. These bicompartmental particles are composed of an interpenetrating polymer network of poly(ethylene oxide) and poly(acrylamide-co-acrylic acid) in one hemisphere and a crosslinked copolymer of dextran and poly(acrylamide-co-acrylic acid) segments in the second compartment. The compositional anisotropy caused differential hydrolytic susceptibility: Although both compartments were stable at pH 3.0, selective degradation of the PEO-containing compartment pH 7.4 was observed within 5 days. Janus particles with differentially degradable polymer compartments may be of interest for a range of oral drug delivery applications because of their propensity for decoupled release profiles.

Compartmentalized photoreactions within compositionally anisotropic Janus microstructures.

We demonstrate spatially controlled photoreactions within bicompartmental microparticles and microfibers. Selective photoreactions are achieved by anisotropic incorporation of photocrosslinkable poly(vinyl cinnamate) in one compartment of either colloids or microfibers. Prior to photoreaction, bicompartmental particles, and fibers were prepared by EHD co-jetting of two compositionally distinct polymer solutions. Physical and chemical anisotropy was confirmed by confocal laser scanning microscopy, Fourier-transformed infrared spectroscopy, and scanning electron microscopy. The data indicate adjustment of polymer concentrations of the jetting solutions to be the determining factors for particle and fiber structures. Subsequent exposure of poly(vinyl cinnamate)-based particles and fibers to UV light at 254 nm resulted in spatially controlled crosslinking. Treatment of the crosslinked bicompartmental colloids with chloroform produced half-moon shaped objects. These hemishells exhibited a distinct porous morphology with pore sizes in the range of 70 nm. Based on this novel synthetic approach, Janus-type particles and fibers can be prepared by EHD co-jetting and can be selectively photocrosslinked without the need for masks or selective laser writing.

Anisotropic hybrid particles based on electrohydrodynamic co-jetting of nanoparticle suspensions.

Electrohydrodynamic co-jetting of two different nanocrystal suspensions can result in anisotropic nanocomposite particles. Using this approach, we are able to prepare submicron-sized, spherical Janus particles (464 ± 242 nm), which are not only comprised of two chemically distinct compartments, but are also morphologically anisotropic. Specifically, multifunctional hybrid particles have been derived, which are composed of a crosslinked copolymer, poly(acrylamide-co-acrylic acid) (p(AAm-co-AA)), and compartmentalized with respect to two metal oxides, i.e. titanium dioxide (TiO(2)) and magnetite (Fe(3)O(4)). Due to size as well as optical color differences between the Fe(3)O(4) (∼10 nm) and TiO(2) (<100 nm) loadings, the surface morphology of the two compartments are significantly different and the particles display magnetic, optical, and interfacial anisotropy. Magnetic anisotropy of the particles has been utilized to control the particles' positioning in an external magnetic field, which--with further work--may lead to magnetically switchable surfaces for display applications.

Compartmentalization of Gold Nanocrystals in Polymer Microparticles using Electrohydrodynamic Co-Jetting.

Polymer particles with micro- and nanoscale anisotropy have received increasing interest for their ability to simultaneously present different physical- and chemical properties. In this communication, we demonstrate that gold nanocrystals (NCs) can be selectively incorporated into one compartment of anisotropic polymer particles. Stable bicompartmental particles were prepared via electrohydrodynamic co-jetting of aqueous nanoparticle suspensions followed by thermal cross-linking. Bicompartmental particle populations with different NC densities were obtained by varying the NC concentration in the jetting suspension. While NC-loaded polymer particles showed different optical properties depending on the NC density, they still maintained discrete interfaces between two compartments. Moreover, the fraction of the bicompartmental particles was higher than 98% based on flow cytometry. This study delineates a new approach for preparation of inorganic/organic composite particles with precisely engineered, anisotropic nanoparticle distributions and may contribute to further developments in emerging scientific areas, such as smart materials or particle-based diagnostics.

Polyurethane with tethered copper(II)-cyclen complex: preparation, characterization and catalytic generation of nitric oxide from S-nitrosothiols.

The preparation and characterization of a commercial biomedical-grade polyurethane (Tecophilic((R)), SP-93A-100) material possessing covalently linked copper(II)-cyclen moieties as a nitric oxide (NO) generating polymer are described. Chemiluminescence NO measurements demonstrate that the prepared polymer can decompose endogenous S-nitrosothiols (RSNOs) such as S-nitrosoglutathione and S-nitrosocysteine to NO in the presence of thiol reducing agents (RSHs; e.g., glutathione and cysteine) at physiological pH. Since such RSNO and RSH species already exist in blood, the proposed polymer is capable of spontaneously generating NO when in contact with fresh blood. This is demonstrated by utilizing the polymer as an outer coating at the distal end of an amperometric NO sensor to create a device that generates response toward the RSNO species in the blood. This polymer possesses the combined benefits of a commercial biomedical-grade polyurethane with the ability to generate biologically active NO when in contact with blood, and thus may serve as a useful coating to improve the hemocompatibility of various medical devices.