Amit Joshi

Characterizing energy dissipation in single-walled carbon nanotube polycarbonate composites

In this study, single-walled carbon nanotube and bisphenol-A-polycarbonate composite beams were fabricated by a solution mixing process and dynamic (cyclic) load tests were performed to characterize energy dissipation. We report up to an order of magnitude (>1000%) increase in loss modulus of the polycarbonate system with the addition of 2% weight fraction of oxidized single-walled nanotube fillers. We show that the increase in damping is derived from frictional sliding at the nanotube-polymer interfaces. The nanoscale dimensions of the tubes not only result in large interfacial contact area, thereby generating high damping efficiency, but also enable seamless integration of the filler materials into the composite structure.

Nanotube-assisted protein deactivation

Conjugating proteins onto carbon nanotubes has numerous applications in biosensing, imaging and cellular delivery. However, remotely controlling the activity of proteins in these conjugates has never been demonstrated. Here we show that upon near-infrared irradiation, carbon nanotubes mediate the selective deactivation of proteins in situ by photochemical effects. We designed nanotube-peptide conjugates to selectively destroy the anthrax toxin, and also optically transparent coatings that can self-clean following either visible or near-infrared irradiation. Nanotube-assisted protein deactivation may be broadly applicable to the selective destruction of pathogens and cells, and will have applications ranging from antifouling coatings to functional proteomics.

Parallel synthesis and screening of polymers for nonviral gene delivery

We describe the parallel synthesis and in vitro evaluation of a cationic polymer library for the discovery of nonviral gene delivery vectors. The library was synthesized based on the ring-opening polymerization reaction between epoxide groups of diglycidyl ethers and the amines of (poly)amines. Parallel screening of soluble library constituents led to the identification of lead polymers with high DNA-binding efficacies. Transfection efficacies of lead polymers were evaluated using PC3-PSMA human prostate cancer cells and murine osteoblasts in the absence and presence of serum. In vitro experiments resulted in the identification of a candidate polymer that demonstrated significantly higher transfection efficacies and lower cytotoxicities than poly(ethyleneimine) (pEI), the current standard for polymeric transfection agents. In addition, polymers that demonstrated moderately higher and comparable transfection efficacies with respect to pEI were also identified. Our results demonstrate that high-throughput synthesis and screening of polymers is a powerful approach for the identification of novel nonviral gene delivery agents.

The Design of Polyvalent Therapeutics

This article reviews recent developments in the design of polyvalent ligands for in vivo applications. Topics discussed include the design of polyvalent inhibitors of toxins and viruses, the use of polyvalency for targeted drug delivery and imaging, and applications of polyvalency for enhancing or suppressing immune responses.

Creep mitigation in composites using carbon nanotube additives

A major limitation of thermosetting epoxy based polymeric materials in long-term structural applications is mechanical creep. Here it is demonstrated that single-walled carbon nanotube additives in low weight fractions (0.1?0.25%) are effective in limiting the load-induced re-orientation of epoxy chains, resulting in a significant slowing of the creep response. Nanotube additives could therefore be the key enabler for the long-term higher-temperature application of polymeric structures which would otherwise fail by excessive creep deformation.

Structure-based Design of a Heptavalent Anthrax Toxin Inhibitor

The design of polyvalent molecules, consisting of multiple copies of a biospecific ligand attached to a suitable scaffold, represents a promising approach to inhibit pathogens and oligomeric microbial toxins. Despite the increasing interest in structure-based drug design, few polyvalent inhibitors based on this approach have shown efficacy in vivo. Here we demonstrate the structure-based design of potent biospecific heptavalent inhibitors of anthrax lethal toxin. Specifically, we illustrate the ability to design potent polyvalent ligands by matching the pattern of binding sites on the biological target. We used a combination of experimental studies based on mutagenesis and computational docking studies to identify the binding site for an inhibitory peptide on the heptameric subunit of anthrax toxin. We developed an approach based on copper-catalyzed azide-alkyne cycloaddition (click-chemistry) to facilitate the attachment of seven copies of the inhibitory peptide to a β-cyclodextrin core via a polyethylene glycol linker of an appropriate length. The resulting heptavalent inhibitors neutralized anthrax lethal toxin both in vitro and in vivo and showed appreciable stability in serum. Given the inherent biocompatibility of cyclodextrin and polyethylene glycol, these potent well-defined heptavalent inhibitors show considerable promise as anthrax antitoxins.

Biomolecule-Nanomaterial Interactions: Effect on Biomolecular Structure, Function, and Stability

We have characterized the influence of protein–carbon nanotube interactions on protein structure and function using various techniques such as Fourier transform infrared spectroscopy, circular dichroism spectroscopy, and atomic force microscopy. This structure-based analysis revealed that different proteins interact with nanotubes differentially, consistent with the observed biological activity data. Furthermore, the high degree of surface curvature of the nanoscale support was found to play an important role in stabilizing proteins under denaturing conditions. Along with these fundamental studies, various applications of such highly active and stable nanotube–protein conjugates have been pursued, which include self-cleaning nanobiocomposite films, interfacial biocatalysis in a biphasic medium, and synthesis of nanotube–nanoparticle hybrids, among others.

Characterizing energy dissipation in singlewalled carbon nanotube polycarbonate composites.

In this study, singlewalled carbon nanotube and bisphenol‐A‐polycarbonate composite beams were fabricated by a solution mixing process and dynamic (cyclic) load tests were performed to characterize energy dissipation. We report up to an order of magnitude (>1000%) increase in loss modulus of the polycarbonate system with the addition of 2% weight fraction of oxidized singlewalled nanotube fillers. We show that the increase in damping is derived from frictional sliding at the nanotube‐polymer interfaces. The nanoscale dimensions of the tubes not only results in large interfacial contact area, thereby generating high damping efficiency, but also enables seamless integration of the filler materials into the composite structure.