Young-wook Jun

Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging

Successful development of ultra-sensitive molecular imaging nanoprobes for the detection of targeted biological objects is a challenging task. Although magnetic nanoprobes have the potential to perform such a role, the results from probes that are currently available have been far from optimal. Here we used artificial engineering approaches to develop innovative magnetic nanoprobes, through a process that involved the systematic evaluation of the magnetic spin, size and type of spinel metal ferrites. These magnetism-engineered iron oxide (MEIO) nanoprobes, when conjugated with antibodies, showed enhanced magnetic resonance imaging (MRI) sensitivity for the detection of cancer markers compared with probes currently available. Also, we successfully visualized small tumors implanted in a mouse. Such high-performance, nanotechnology-based molecular probes could enhance the ability to visualize other biological events critical to diagnostics and therapeutics.

Observation of Single Colloidal Platinum Nanocrystal Growth Trajectories

Mergers and Acquisitions The crystallization of small molecules or polymers is often described in terms of a nucleation stage, where initial clusters form, followed by a distinct growth stage. Growth can come from the addition of unbound molecules, or through “Ostwald ripening” where larger crystals grow at the expense of smaller ones due to thermodynamic effects. Zheng et al. (p. 1309) studied the growth of platinum nanocrystals inside a transmission electron microscope using a special liquid cell, allowing observation of crystal growth in situ. Both monomer addition to growing particles and the coalescence of two particles were observed. The specific growth mechanism appeared to be governed by the size of each of the particles. The combination of growth processes makes it possible for an initially broad distribution of particles to narrow into an almost uniform one. Transmission electron microscopy provides details of the growth mechanisms of platinum nanocrystals in solution. Understanding of colloidal nanocrystal growth mechanisms is essential for the syntheses of nanocrystals with desired physical properties. The classical model for the growth of monodisperse nanocrystals assumes a discrete nucleation stage followed by growth via monomer attachment, but has overlooked particle-particle interactions. Recent studies have suggested that interactions between particles play an important role. Using in situ transmission electron microscopy, we show that platinum nanocrystals can grow either by monomer attachment from solution or by particle coalescence. Through the combination of these two processes, an initially broad size distribution can spontaneously narrow into a nearly monodisperse distribution. We suggest that colloidal nanocrystals take different pathways of growth based on their size- and morphology-dependent internal energies.

Chemical Design of Nanoparticle Probes for High-Performance Magnetic Resonance Imaging

Synthetic magnetic nanoparticles (MNPs) are emerging as versatile probes in biomedical applications, especially in the area of magnetic resonance imaging (MRI). Their size, which is comparable to biological functional units, and their unique magnetic properties allow their utilization as molecular imaging probes. Herein, we present an overview of recent breakthroughs in the development of new synthetic MNP probes with which the sensitive and target-specific observation of biological events at the molecular and cellular levels is possible.

Nanoscaling Laws of Magnetic Nanoparticles and Their Applicabilities in Biomedical Sciences

Magnetic nanoparticles, which exhibit a variety of unique magnetic phenomena that are drastically different from those of their bulk counterparts, are garnering significant interest since these properties can be advantageous for utilization in a variety of applications ranging from storage media for magnetic memory devices to probes and vectors in the biomedical sciences. In this Account, we discuss the nanoscaling laws of magnetic nanoparticles including metals, metal ferrites, and metal alloys, while focusing on their size, shape, and composition effects. Their fundamental magnetic properties such as blocking temperature (Tb), spin life time (tau), coercivity (Hc), and susceptibility (chi) are strongly influenced by the nanoscaling laws, and as a result, these scaling relationships can be leveraged to control magnetism from the ferromagnetic to the superparamagnetic regimes. At the same time, they can be used in order to tune magnetic values including Hc, chi, and remanence (Mr). For example, life time of magnetic spin is directly related to the magnetic anisotropy energy (KuV) and also the size and volume of nanoparticles. The blocking temperature (Tb) changes from room temperature to 10 K as the size of cobalt nanoparticles is reduced from 13 to 2 nm. Similarly, H c is highly susceptible to the anisotropy of nanoparticles, while saturation magnetization is directly related to the canting effects of the disordered surface magnetic spins and follows a linear relationship upon plotting of ms (1/3) vs r(-1). Therefore, the nanoscaling laws of magnetic nanoparticles are important not only for understanding the behavior of existing materials but also for developing novel nanomaterials with superior properties. Since magnetic nanoparticles can be easily conjugated with biologically important constituents such as DNA, peptides, and antibodies, it is possible to construct versatile nano-bio hybrid particles, which simultaneously possess magnetic and biological functions for biomedical diagnostics and therapeutics. As demonstrated in this Account, nanoscaling laws for magnetic components are found to be critical to the design of optimized magnetic characteristics of hybrid nanoparticles and their enhanced applicability in the biomedical sciences including their utilizations as contrast enhancement agents for magnetic resonance imaging (MRI), ferromagnetic components for nano-bio hybrid structures, and translational vectors for magnetophoretic sensing of biological species. In particular, systematic modulation of saturation magnetization of nanoparticle probes is important to maximize MR contrast effects and magnetic separation of biological targets.

Coupling of Optical Resonances in a Compositionally Asymmetric Plasmonic Nanoparticle Dimer

Electromagnetic coupling between plasmon resonant nanoparticles follows principles of molecular hybridization, that is, particle plasmons hybridize to form a lower energy bonding plasmon mode and a higher energy antibonding plasmon mode. For coupling between equivalent particles (homodimer), the in-phase mode is optically allowed, whereas the out-of-phase mode is dark due to the cancellation of the equivalent dipole moments. We probe, using polarized scattering spectroscopy, the coupling in a pair of nonequivalent particles (silver/gold nanoparticle heterodimer) that allows us to observe both in-phase and out-of-phase plasmon modes. The hybridization model postulates that the bonding modes should be red shifted with respect to the gold particle plasmon resonance and the antibonding modes blue shifted with respect to the silver particle plasmon resonance. In practice, the antibonding modes are red shifted with respect to the silver plasmon resonance. This anomalous shift is due to the coupling of the silver particle plasmon resonance to the quasi-continuum of interband transitions in gold, which dominate in the spectral region of the silver particle plasmon resonance. The hybridization model, which considers only free-electron behavior of the metals, fails to account for this coupling.

Heterostructured magnetic nanoparticles: their versatility and high performance capabilities

Magnetic nanoparticles exhibit unique nanoscale properties and their utilization for various magnetic systems is of significant interest. Especially, heterostructured magnetic nanoparticles are emerging as next-generation materials due to their synergistically enhanced magnetism and potential multifunctionalities. Herein, we overview the recent advances in the development of magnetic nanoparticles with a focus on multicomponent heterostructured nanoparticles including alloys, core-shells, and binary superlattices synthesized via nonhydrolytic methods. Their multifunctionalites and high performance capabilities are demonstrated for applications in high density magnetic storages, chemical catalysis, and biomedical separation and diagnostics.

Hetero-Epitaxial Anion Exchange Yields Single-Crystalline Hollow Nanoparticles

Anion exchange with S was performed on ZnO colloidal nanoparticles. The resulting hollow ZnS nanoparticles are crystal whose shape is dictated by the initial ZnO. Crystallographic and elemental analyses provide insight into the mechanism of the anion exchange.

Continuous imaging of plasmon rulers in live cells reveals early-stage caspase-3 activation at the single-molecule level

The use of plasmon coupling in metal nanoparticles has shown great potential for the optical characterization of many biological processes. Recently, we have demonstrated the use of “plasmon rulers” to observe conformational changes of single biomolecules in vitro. Plasmon rulers provide robust signals without photobleaching or blinking. Here, we show the first application of plasmon rulers to in vivo studies to observe very long trajectories of single biomolecules in live cells. We present a unique type of plasmon ruler comprised of peptide-linked gold nanoparticle satellites around a core particle, which was used as a probe to optically follow cell-signaling pathways in vivo at the single-molecule level. These “crown nanoparticle plasmon rulers” allowed us to continuously monitor trajectories of caspase-3 activity in live cells for over 2 h, providing sufficient time to observe early-stage caspase-3 activation, which was not possible by conventional ensemble analyses.

Formation of targeted monovalent quantum dots by steric exclusion

Precise control over interfacial chemistry between nanoparticles and other materials remains a significant challenge limiting the broad application of nanotechnology in biology. To address this challenge, we use “Steric Exclusion” to completely convert commercial quantum dots (QDs) into monovalent imaging probes by wrapping the QD with a functionalized oligonucleotide. We demonstrate the utility of these QDs as modular and non-perturbing imaging probes by tracking individual Notch receptors on live cells.

A Mechanogenetic Toolkit for Interrogating Cell Signaling in Space and Time

Tools capable of imaging and perturbing mechanical signaling pathways with fine spatiotemporal resolution have been elusive, despite their importance in diverse cellular processes. The challenge in developing a mechanogenetic toolkit (i.e., selective and quantitative activation of genetically encoded mechanoreceptors) stems from the fact that many mechanically activated processes are localized in space and time yet additionally require mechanical loading to become activated. To address this challenge, we synthesized magnetoplasmonic nanoparticles that can image, localize, and mechanically load targeted proteins with high spatiotemporal resolution. We demonstrate their utility by investigating the cell-surface activation of two mechanoreceptors: Notch and E-cadherin. By measuring cellular responses to a spectrum of spatial, chemical, temporal, and mechanical inputs at the single-molecule and single-cell levels, we reveal how spatial segregation and mechanical force cooperate to direct receptor activation dynamics. This generalizable technique can be used to control and understand diverse mechanosensitive processes in cell signaling. VIDEO ABSTRACT.