Mrinmoy De

Gold nanoparticles in delivery applications

Gold nanoparticles (AuNPs) provide non-toxic carriers for drug and gene delivery applications. With these systems, the gold core imparts stability to the assembly, while the monolayer allows tuning of surface properties such as charge and hydrophobicity. An additional attractive feature of AuNPs is their interaction with thiols, providing an effective and selective means of controlled intracellular release.

Sensing of proteins in human serum using conjugates of nanoparticles and green fluorescent protein

There is a direct correlation between protein levels and disease states in human serum making it an attractive target for sensors and diagnostics. However this is made challenging because serum features more than 20,000 proteins with an overall protein content of greater than 1 mM. Here we report a hybrid synthetic-biomolecule based sensor that uses green fluorescent protein-nanoparticle arrays to detect proteins at biorelevant concentrations in both buffer and human serum. Distinct and reproducible fluorescence response patterns were obtained from five serum proteins (human serum albumin, immunoglobulin G, transferrin, fibrinogen and α-antitrypsin) in buffer and when spiked into human serum. Using linear discriminant analysis we identified these proteins with an identification accuracy of 100% in buffer and 97% in human serum. The arrays were also able to discriminate between different concentrations of the same protein as well as a mixture of different proteins in human serum.There is a direct correlation between protein levels and disease states in human serum, which makes it an attractive target for sensors and diagnostics. However, this is challenging because serum features more than 20,000 proteins, with an overall protein content greater than 1 mM. Here we report a sensor based on a hybrid synthetic-biomolecule that uses arrays of green fluorescent protein and nanoparticles to detect proteins at biorelevant concentrations in both buffer and human serum. Distinct and reproducible fluorescence-response patterns were obtained from five serum proteins (human serum albumin, immunoglobulin G, transferrin, fibrinogen and a-antitrypsin), both in buffer and when spiked into human serum. Using linear discriminant analysis we identified these proteins with an identification accuracy of 100% in buffer and 97% in human serum. The arrays were also able to discriminate between different concentrations of the same protein, as well as a mixture of different proteins in human serum.

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.

Core-controlled polymorphism in virus-like particles

This study concerns the self-assembly of virus-like particles (VLPs) composed of an icosahedral virus protein coat encapsulating a functionalized spherical nanoparticle core. The recent development of efficient methods for VLP self-assembly has opened the way to structural studies. Using electron microscopy with image reconstruction, the structures of several VLPs obtained from brome mosaic virus capsid proteins and gold nanoparticles were elucidated. Varying the gold core diameter provides control over the capsid structure. The number of subunits required for a complete capsid increases with the core diameter. The packaging efficiency is a function of the number of capsid protein subunits per gold nanoparticle. VLPs of varying diameters were found to resemble to three classes of viral particles found in cells (T = 1, 2, and 3). As a consequence of their regularity, VLPs form three-dimensional crystals under the same conditions as the wild-type virus. The crystals represent a form of metallodielectric material that exhibits optical properties influenced by multipolar plasmonic coupling.

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.

Role of Surface Charge Density in Nanoparticle-Templated Assembly of Bromovirus Protein Cages

Self-assembling icosahedral protein cages have potentially useful physical and chemical characteristics for a variety of nanotechnology applications, ranging from therapeutic or diagnostic vectors to building blocks for hierarchical materials. For application-specific functional control of protein cage assemblies, a deeper understanding of the interaction between the protein cage and its payload is necessary. Protein-cage encapsulated nanoparticles, with their well-defined surface chemistry, allow for systematic control over key parameters of encapsulation such as the surface charge, hydrophobicity, and size. Independent control over these variables allows experimental testing of different assembly mechanism models. Previous studies done with Brome mosaic virus capsids and negatively charged gold nanoparticles indicated that the result of the self-assembly process depends on the diameter of the particle. However, in these experiments, the surface-ligand density was maintained at saturation levels, while the total charge and the radius of curvature remained coupled variables, making the interpretation of the observed dependence on the core size difficult. The current work furnishes evidence of a critical surface charge density for assembly through an analysis aimed at decoupling the surface charge and the core size.

Towards Non-Invasive Diagnostic Imaging of Early-Stage Alzheimer’s Disease

One way to image the molecular pathology in Alzheimer’s disease (AD) is by positron emission tomography using probes that target amyloid fibrils. However, these fibrils are not closely linked to the development of the disease. It is now thought that early stage biomarkers that instigate memory loss comprise of Aβ oligomers (AβOs). Here we report a sensitive molecular magnetic resonance imaging (MRI) contrast probe that is specific for AβOs. We attach oligomer-specific antibodies onto magnetic nanostructures and show the complex is stable and it binds to AβOs on cells and brain tissues to give a MRI signal. When intranasally administered to an AD mouse model, the probe readily reached hippocampal AβOs. In isolated samples of human brain tissue, we observed an MRI signal that distinguished AD from controls. Such nanostructures that target neurotoxic AβOs are potentially useful for evaluating the efficacy of new drugs and ultimately for early-stage AD diagnosis and disease management.