Structural interactions in polymer-stabilized magnetic nanocomposites.

Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted significant attention because of their nanoscale magnetic properties. SPION aggregates may afford emergent properties, resulting from dipole-dipole interactions between neighbors. Such aggregates can display internal order, with high packing fractions (>20%), and can be stabilized with block co-polymers (BCPs), permitting design of tunable composites for potential nanomedicine, data storage, and electronic sensing applications. Despite the routine use of magnetic fields for aggregate actuation, the impact of those fields on polymer structure, SPION ordering, and magnetic properties is not fully understood. Here, we report that external magnetic fields can induce ordering in SPION aggregates that affect their structure, inter-SPION distance, magnetic properties, and composite Tg. SPION aggregates were synthesized in the presence or absence of magnetic fields or exposed to magnetic fields post-synthesis. They were characterized using transmission electron microscopy (TEM), small angle X-ray scattering (SAXS), superconducting quantum interference device (SQUID) analysis, and differential scanning calorimetry (DSC). SPION aggregate properties depended on the timing of field application. Magnetic field application during synthesis encouraged preservation of SPION chain aggregates stabilized by polymer coatings even after removal of the field, whereas post synthesis application triggered subtle internal reordering, as indicated by increased blocking temperature (TB), that was not observed via SAXS or TEM. These results suggest that magnetic fields are a simple, yet powerful tool to tailor the structure, ordering, and magnetic properties of polymer-stabilized SPION nanocomposites.

Nanoparticle packing within block copolymer micelles prepared by the interfacial instability method.

The interfacial instability method has emerged as a viable approach for encapsulating high concentrations of nanoparticles (NPs) within morphologically diverse micelles. In this method, transient interfacial instabilities at the surface of an emulsion droplet guide self-assembly of block co-polymers and NP encapsulants. Although used by many groups, there are no systematic investigations exploring the relationship between NP properties and micelle morphology. Here, the effect of quantum dot (QD) and superparamagnetic iron oxide NP (SPION) concentration on the shape, size, and surface deformation of initially spherical poly(styrene-b-ethylene oxide) (PS-b-PEO) micelles was examined. Multi-NP encapsulation and uniform dispersion within micelles was obtained even at low NP concentrations. Increasing NP concentration initially resulted in larger numbers of elongated micelles and cylinders with tightly-controlled diameters smaller than those of spherical micelles. Beyond a critical NP concentration, micelle formation was suppressed; the dominant morphology became densely-loaded NP structures that were coated with polymer and exhibited increased polydispersity. Transmission electron microscopy (TEM) and small angle X-ray scattering (SAXS) revealed that NPs in densely-loaded structures can be well-ordered, with packing volume fractions of up to 24%. These effects were enhanced in magnetic composites, possibly by dipole interactions. Mechanisms governing phase transitions triggered by NP loading in the interfacial instability process were proposed. The current study helps establish and elucidate the active role played by NPs in directing block copolymer assembly in the interfacial instability process, and provides important guiding principles for the use of this approach in generating NP-loaded block copolymer composites.

Morphology of block copolymer micelles formed via electrospray enabled interfacial instability.

HYPOTHESIS: Elongated micelles may be preferred over spherical because of their increased loading capacity, differential mass transport and biodistribution. Although morphological transitions of block co-polymer (BCP) micelles have been extensively investigated in batch systems, research on continuous or semi-continuous scalable approaches such as flash nanoprecipitation and coaxial electrospray-enabled interfacial instability (Aero-IS) have primarily focused on producing spherical micelles. This paper investigates whether process changes intended to increase micelle production via Aero-IS also induce morphological transitions. EXPERIMENTS: BCP micelles were synthesized from carboxylated polystyrene-block-poly(ethylene oxide) (PS-b-PEO) (PS 9.5 kDa:PEO 18.0 kDa) using Aero-IS. Volumetric flowrates, polymer concentrations, and emulsion temperature were varied to investigate their effect on the micelle production rate and resulting micelle structure, including transitions to worm-like micelles. FINDINGS: These findings report the first worm-like micelles formed via a scalable, interfacial instability approach. The morphological transitions obtained by increasing polymer concentration occurred at lower nominal values than in corresponding batch processes. Optimizing operating conditions also led to a 12-fold increase in micelle production rates over prior electrospray reports (Duong, 2014). Thus, the Aero-IS approach holds promise for scalable nanomanufacturing of worm-like micelles, potentially enabling applications in drug delivery, imaging, diagnostics, and separations.

Micelle-templated, poly(lactic-co-glycolic acid) nanoparticles for hydrophobic drug delivery.

PURPOSE: Poly(lactic-co-glycolic acid) (PLGA) is widely used for drug delivery because of its biocompatibility, ability to solubilize a wide variety of drugs, and tunable degradation. However, achieving sub-100 nm nanoparticles (NPs), as might be desired for delivery via the enhanced permeability and retention effect, is extremely difficult via typical top-down emulsion approaches. METHODS: Here, we present a bottom-up synthesis method yielding PLGA/block copolymer hybrids (ie, "PolyDots"), consisting of hydrophobic PLGA chains entrapped within self-assembling poly(styrene-b-ethylene oxide) (PS-b-PEO) micelles. RESULTS: PolyDots exhibit average diameters <50 nm and lower polydispersity than conventional PLGA NPs. Drug encapsulation efficiencies of PolyDots match conventional PLGA NPs (ie, ~30%) and are greater than those obtained from PS-b-PEO micelles (ie, ~7%). Increasing the PLGA:PS-b-PEO weight ratio alters the drug release mechanism from chain relaxation to erosion controlled. PolyDots are taken up by model glioma cells via endocytotic mechanisms within 24 hours, providing a potential means for delivery to cytoplasm. PolyDots can be lyophilized with minimal change in morphology and encapsulant functionality, and can be produced at scale using electrospray. CONCLUSION: Encapsulation of PLGA within micelles provides a bottom-up route for the synthesis of sub-100 nm PLGA-based nanocarriers with enhanced stability and drug-loading capacity, and tunable drug release, suitable for potential clinical applications.

Mechanotransduction Effects on Endothelial Cell Proliferation via CD31 and VEGFR2: Implications for Immunomagnetic Separation.

Immunomagnetic separation is used to isolate circulating endothelial cells (ECs) and endothelial progenitor cells (EPCs) for diagnostics and tissue engineering. However, potentially detrimental changes in cell properties have been observed post-separation. Here, the effect of mechanical force, which is naturally applied during immunomagnetic separation, on proliferation of human umbilical vein endothelial cells (HUVEC), kinase insert domain-positive receptor (KDR) cells, and peripheral blood mononuclear cells (PBMCs). Cells are exposed to CD31 or Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) targeted MACSi beads at varying bead to cell ratios and compared to free antibody and unconjugated beads. A vertical magnetic gradient is applied to static 2D cultures, and a magnetic cell sorter is used to analyze cells in dynamic flow. No significant difference in EC proliferation is observed for controls or VEGFR2-targeting beads, whereas CD31-conjugated beads increase proliferation in a dose dependent manner in static 2-D cultures. This effect occurs in the absence of magnetic field, but is more pronounced with magnetic force. After flow sorting, similar increases in proliferation are seen for CD31 targeting beads. Thus, the effects of targeting antibody and magnetic force applied should be considered when designing immunomagnetic separation protocols for ECs.