Gang Ruan

Scalable, Semicontinuous Production of Micelles Encapsulating Nanoparticles via Electrospray

Nanoparticle encapsulation within micelles has been demonstrated as a versatile platform for creating water-soluble nanocomposites. However, in contrast to typical micelle encapsulants, such as small molecule drugs and proteins, nanoparticles are substantially larger, which creates significant challenges in micelle synthesis, especially at large scale. Here, we describe a new nanocomposite synthesis method that combines electrospray, a top-down, continuous manufacturing technology currently used for polymer microparticle fabrication, with bottom-up micellar self-assembly to yield a scalable, semicontinuous micelle synthesis method: i.e., micellar electrospray. Empty micelles and micellar nanocomposites containing quantum dots (QDs), superparamagnetic iron oxide nanoparticles (SPIONs), and their combination were produced using micellar electrospray with a 30-fold increase in yield by weight over batch methods. Particles were characterized using dynamic light scattering, transmission electron microscopy, and scanning mobility particle sizing, with remarkable agreement between methods, which indicated size distributions with variations of as little as ~5%. In addition, new methodologies for qualitatively evaluating nanoparticle loading in the resultant micelles are presented. Micellar electrospray is a broad, scalable nanomanufacturing approach that should be easily adapted to virtually any hydrophobic molecule or nanoparticle with a diameter smaller than the micelle core, potentially enabling synthesis of a vast array of nanocomposites and self-assembled nanostructures.

Magnetic quantum dots in biotechnology – synthesis and applications

Quantum dots (QDs) have great promise in biological imaging, and as this promise is realized, there has been increasing interest in combining the benefits of QDs with those of other materials to yield composites with multifunctional properties. One of the most common materials combined with QDs is magnetic materials, either as ions (e.g. gadolinium) or as nanoparticles (e.g. superparamagnetic iron oxide nanoparticles, SPIONs). The fluorescent property of the QDs permits visualization, whereas the magnetic property of the composite enables imaging, magnetic separation, and may even have therapeutic benefit. In this review, the synthesis of fluorescent–magnetic nanoparticles, including magnetic QDs is explored; and the applications of these materials in imaging, separations, and theranostics are discussed. As the properties of these materials continue to improve, QDs have the potential to greatly impact biological imaging, diagnostics, and treatment.

Microparticles and Nanoparticles

Microparticles and nanoparticles have had an enormous impact on a wide-range of biomedical applications including drug delivery, imaging, and basic research. Miniaturization of therapeutic devices to the micron (1–1000 μm), sub-micron (100–1000 nm), and nanometer (1–100 nm) scales has facilitated the integration of biomedical devices with therapeutic biomolecules for improved clinical efficacy. Despite their identical composition to bulk materials, microparticles and nanoparticles represent a new class of biomaterials with distinct properties, interactions with biological components, and distribution within the body. Microparticles are most commonly employed in drug and vaccine delivery. Nanomaterials represent an emerging field; careful study of their biological activity will be required before there is large-scale clinical application.

Fluorescent–magnetic nanoparticles for imaging and cell manipulation

Individual classes of nanoparticles have made a tremendous impact on the biomedical sciences, with advances in imaging, single-molecule tracking, and cellular mechanotransduction. However, the future of nanotechnology will probably depend on the combination of attributes from several different nanomaterials. Here, one class of hybrid nanoparticles that possess both fluorescent and magnetic functionalities is described. These nanocomposites are created by combining fluorescent nanoparticles with magnetic iron oxide nanoparticles in an encapsulating micelle or solid polymer sphere. The resulting composites range from 10 to 500nm in size and display both fluorescent and magnetic properties of the constituent nano-particles. These particles are demonstrated as in vitro cellular labels, aprecursor to future in vivo studies; they will expand in vivo imaging options by providing the capability for both magnetic resonance (MR) and fluorescence imaging.

Synthesis and manipulation of multifunctional, fluorescent-magnetic nanoparticles for single molecule tracking

Heterogeneous nanostructures that possess multiple properties as a result of their differing constituent materials have attracted significant interest in the last few years. In particular, fluorescent-magnetic nanostructures have potential applications in imaging, separations, and single molecule tracking as a result of their fluorescent and magnetic properties. Here we report the synthesis of fluorescent-magnetic nanocomposites composed of fluorescent semiconductor quantum dots or graphitic carbon nanoparticles and magnetic iron oxide nanoparticles. We have developed synthetic strategies using either micellular or polymer encapsulation, yielding composites from ~10 - 100s of nms. Composites maintain the fluorescent and magnetic properties of their constituent materials. These composites can be used for in vitro and in vivo imaging using fluorescent or magnetic (e.g., MRI) modalities. Additionally, we describe the manipulation of these composites using magnetic instrumentation. In particular, we have designed a magnetic needle that can be used to manipulate nanocomposites. Particles as small as 30 nm can be manipulated while simultaneous observed through their fluorescent property. Single particle status can be confirmed through quantum dot blinking, demonstrating the potential of these composites for single molecule tracking.