Stanley S. Chou

Chemically exfoliated MoS2 as near-infrared photothermal agents.

The near-infrared (NIR) window refers to a range of wavelengths (700–1300 nm) in which biological tissues are highly transparent.[1] Consequently, biological imaging and therapy modalities employ light at these wavelengths for the monitoring[1] and triggering[2] of biological events in vitro and in vivo. For instance, photothermal ablation takes advantage of NIR absorbing materials for transducing light into heat.[2] The resultant thermal energy can be used for a number of applications, such as tissue ablation and drug release. Despite the intense interest in NIR photothermal agents, their development has suffered from considerable challenges. In particular, few nanomaterials display the requisite absorption profiles required for NIR photothermal transduction.

Ligand Conjugation of Chemically Exfoliated MoS2

MoS2 is a two-dimensional material that is gaining prominence due to its unique electronic and chemical properties. Here, we demonstrate ligand conjugation of chemically exfoliated MoS2 using thiol chemistry. With this method, we modulate the ζ-potential and colloidal stability of MoS2 sheets through ligand designs, thus enabling its usage as a selective artificial protein receptor for β-galactosidase. The facile thiol functionalization route opens the door for surface modifications of solution processable MoS2 sheets.

Nanoscale Graphene Oxide (nGO) as Artificial Receptors: Implications for Biomolecular Interactions and Sensing

The role of conventional graphene-oxide in biosensing has been limited to that of a quenching substrate or signal transducer due to size inconsistencies and poor supramolecular response. We overcame these issues by using nanoscale GOs (nGO) as artificial receptors. Unlike conventional GO, nGOs are sheets with near uniform lateral dimension of 20 nm. Due to its nanoscale architecture, its supramolecular response was enhanced, with demonstrated improvements in biomacromolecular affinities. This rendered their surface capable of detecting unknown proteins with cognizance not seen with conventional GOs. Different proteins at 100 and 10 nM concentrations revealed consistent patterns that are quantitatively differentiable by linear discriminant analysis. Identification of 48 unknowns in both concentrations demonstrated a >95% success rate. The 10 nM detection represents a 10-fold improvement over analogous arrays. This demonstrates for the first time that the supramolecular chemistry of GO is highly size dependent and opens the possibility of improvement upon existing GO hybrid materials.

Enhanced Field‐Emission Behavior of Layered MoS2 Sheets

Field emission studies are reported for the first time on layered MoS₂ sheets at the base pressure of ∼1 × 10⁻⁸ mbar. The turn-on field required to draw a field emission current density of 10 μA/cm² is found to be 3.5 V/μm for MoS₂ sheets. The turn-on values are found to be significantly lower than the reported MoS₂ nanoflowers, graphene, and carbon nanotube-based field emitters due to the high field enhancement factor (∼1138) associated with nanometric sharp edges of MoS₂ sheet emitter surface. The emission current-time plots show good stability over a period of 3 h. Owing to the low turn-on field and planar (sheetlike) structure, the MoS₂ could be utilized for future vacuum microelectronics/nanoelectronic and flat panel display applications.

Graphene oxide as an enzyme inhibitor: modulation of activity of α-chymotrypsin.

We have investigated the efficacy of graphene oxide (GO) in modulating enzymatic activity. Specifically, we have shown that GO can act as an artificial receptor and inhibit the activity of α-chymotrypsin (ChT), a serine protease. Most significantly, our data demonstrate that GO exhibits the highest inhibition dose response (by weight) for ChT inhibition compared with all other reported artificial inhibitors. Through fluorescence spectroscopy and circular dichroism studies, we have shown that this protein-receptor interaction is highly biocompatible and conserves the proteins secondary structure over extended periods (>24 h). We have also explored GO-enzyme interactions by controlling the ionic strength of the medium, which attenuates the host-guest electrostatic interactions. These findings suggest a new generation of enzymatic inhibitors that can be applied to other complex proteins by systematic modification of the GO functionality.

Understanding catalysis in a multiphasic two-dimensional transition metal dichalcogenide

Establishing processing–structure–property relationships for monolayer materials is crucial for a range of applications spanning optics, catalysis, electronics and energy. Presently, for molybdenum disulfide, a promising catalyst for artificial photosynthesis, considerable debate surrounds the structure/property relationships of its various allotropes. Here we unambiguously solve the structure of molybdenum disulfide monolayers using high-resolution transmission electron microscopy supported by density functional theory and show lithium intercalation to direct a preferential transformation of the basal plane from 2H (trigonal prismatic) to 1T′ (clustered Mo). These changes alter the energetics of molybdenum disulfide interactions with hydrogen (ΔGH), and, with respect to catalysis, the 1T′ transformation renders the normally inert basal plane amenable towards hydrogen adsorption and hydrogen evolution. Indeed, we show basal plane activation of 1T′ molybdenum disulfide and a lowering of ΔGH from +1.6 eV for 2H to +0.18 eV for 1T′, comparable to 2H molybdenum disulfide edges on Au(111), one of the most active hydrogen evolution catalysts known.

Controlling the Metal to Semiconductor Transition of MoS2 and WS2 in Solution

Lithiation-exfoliation produces single to few-layered MoS2 and WS2 sheets dispersible in water. However, the process transforms them from the pristine semiconducting 2H phase to a distorted metallic phase. Recovery of the semiconducting properties typically involves heating of the chemically exfoliated sheets at elevated temperatures. Therefore, it has been largely limited to sheets deposited on solid substrates. Here, we report the dispersion of chemically exfoliated MoS2 sheets in high boiling point organic solvents enabled by surface functionalization and the controllable recovery of their semiconducting properties directly in solution. This process connects the scalability of chemical exfoliation with the simplicity of solution processing, ultimately enabling a facile method for tuning the metal to semiconductor transitions of MoS2 and WS2 within a liquid medium.

Hybrid magnetic nanostructures (MNS) for magnetic resonance imaging applications.

The development of MRI contrast agents has experienced its version of the gilded age over the past decade, thanks largely to the rapid advances in nanotechnology. In addition to progress in single mode contrast agents, which ushered in unprecedented R(1) or R(2) sensitivities, there has also been a boon in the development of agents covering more than one mode of detection. These include T(1)-PET, T(2)-PET T(1)-optical, T(2)-optical, T(1)-T(2) agents and many others. In this review, we describe four areas which we feel have experienced particular growth due to nanotechnology, specifically T(2) magnetic nanostructure development, T(1)/T(2)-optical dual mode agents, and most recently the T(1)-T(2) hybrid imaging systems. In each of these systems, we describe applications including in vitro, in vivo usage and assay development. In all, while the benefits and drawbacks of most MRI contrast agents depend on the application at hand, the recent development in multimodal nanohybrids may curtail the shortcomings of single mode agents in diagnostic and clinical settings by synergistically incorporating functionality. It is hoped that as nanotechnology advances over the next decade, it will produce agents with increased diagnostics and assay relevant capabilities in streamlined packages that can meaningfully improve patient care and prognostics. In this review article, we focus on T(2) materials, its surface functionalization and coupling with optical and/or T(1) agents.

Thermoresponsive magnetic hydrogels as theranostic nanoconstructs.

We report the development of thermoresponsive magnetic hydrogels based on poly(N-isopropylacrylamide) encapsulation of Fe3O4 magnetic nanostructures (MNS). In particular, we examined the effects of hydrogels encapsulated with poly-ethylene glycol (PEG) and polyhedral oligomeric silsesquioxane (POSS) surface modified Fe3O4 MNS on magnetic resonance (MR) T2 (transverse spin relaxation) contrast enhancement and associated delivery efficacy of absorbed therapeutic cargo. The microstructural characterization reveal the regular spherical shape and size (∼200 nm) of the hydrogels with elevated hydrophilic to hydrophobic transition temperature (∼40 °C) characterized by LCST (lower critical solution temperature) due to the presence of encapsulated MNS. The hydrogel-MNS (HGMNS) system encapsulated with PEG functionalized Fe3O4 of 12 nm size (HGMNS-PEG-12) exhibited relaxivity rate (r2) of 173 mM–1s–1 compared to 129 mM–1s–1 obtained for hydrogel-MNS system encapsulated with POSS functionalized Fe3O4 (HGMNS-POSS-12) of the same size. Further studies with HGMNS-PEG-12 with absorbed drug doxorubicin (DOX) reveals approximately two-fold enhance in release during 1 h RF (radio-frequency) field exposure followed by 24 h incubation at 37 °C. Quantitatively, it is 2.1 μg mg–1 (DOX/HGMNS) DOX release with RF exposure while only 0.9 μg mg–1 release without RF exposure for the same period of incubation. Such enhanced release of therapeutic cargo is attributed to micro-environmental heating in the surroundings of MNS as well as magneto-mechanical vibrations under high frequency RF inside hydrogels. Similarly, RF-induced in vitro localized drug delivery studies with HeLa cell lines for HGMNS-PEG-12 resulted in more than 80% cell death with RF field exposures for 1 h. We therefore believe that magnetic hydrogel system has in vivo theranostic potential given high MR contrast enhancement from encapsulated MNS and RF-induced localized therapeutic delivery in one nanoconstruct.

Mesoporous Silica Nanoparticle-Supported Lipid Bilayers (Protocells) for Active Targeting and Delivery to Individual Leukemia Cells

Many nanocarrier cancer therapeutics currently under development, as well as those used in the clinical setting, rely upon the enhanced permeability and retention (EPR) effect to passively accumulate in the tumor microenvironment and kill cancer cells. In leukemia, where leukemogenic stem cells and their progeny circulate within the peripheral blood or bone marrow, the EPR effect may not be operative. Thus, for leukemia therapeutics, it is essential to target and bind individual circulating cells. Here, we investigate mesoporous silica nanoparticle (MSN)-supported lipid bilayers (protocells), an emerging class of nanocarriers, and establish the synthesis conditions and lipid bilayer composition needed to achieve highly monodisperse protocells that remain stable in complex media as assessed in vitro by dynamic light scattering and cryo-electron microscopy and ex ovo by direct imaging within a chick chorioallantoic membrane (CAM) model. We show that for vesicle fusion conditions where the lipid surface area exceeds the external surface area of the MSN and the ionic strength exceeds 20 mM, we form monosized protocells (polydispersity index <0.1) on MSN cores with varying size, shape, and pore size, whose conformal zwitterionic supported lipid bilayer confers excellent stability as judged by circulation in the CAM and minimal opsonization in vivo in a mouse model. Having established protocell formulations that are stable colloids, we further modified them with anti-EGFR antibodies as targeting agents and reverified their monodispersity and stability. Then, using intravital imaging in the CAM, we directly observed in real time the progression of selective targeting of individual leukemia cells (using the established REH leukemia cell line transduced with EGFR) and delivery of a model cargo. Overall, we have established the effectiveness of the protocell platform for individual cell targeting and delivery needed for leukemia and other disseminated disease.