Shashank Saraf

The induction of angiogenesis by cerium oxide nanoparticles through the modulation of oxygen in intracellular environments

Angiogenesis is the formation of new blood vessels from existing blood vessels and is critical for many physiological and pathophysiological processes. In this study we have shown the unique property of cerium oxide nanoparticles (CNPs) to induce angiogenesis, observed using both in vitro and in vivo model systems. In particular, CNPs trigger angiogenesis by modulating the intracellular oxygen environment and stabilizing hypoxia inducing factor 1α endogenously. Furthermore, correlations between angiogenesis induction and CNPs physicochemical properties including: surface Ce(3+)/Ce(4+) ratio, surface charge, size, and shape were also explored. High surface area and increased Ce(3+)/Ce(4+) ratio make CNPs more catalytically active towards regulating intracellular oxygen, which in turn led to more robust induction of angiogenesis. Atomistic simulation was also used, in partnership with in vitro and in vivo experimentation, to reveal that the surface reactivity of CNPs and facile oxygen transport promotes pro-angiogenesis.

Fabricated micro-nano devices for in vivo and in vitro biomedical applications.

In recent years, the innovative use of microelectromechanical systems (MEMSs) and nanoelectromechanical systems (NEMSs) in biomedical applications has opened wide opportunities for precise and accurate human diagnostics and therapeutics. The introduction of nanotechnology in biomedical applications has facilitated the exact control and regulation of biological environments. This ability is derived from the small size of the devices and their multifunctional capabilities to operate at specific sites for selected durations of time. Researchers have developed wide varieties of unique and multifunctional MEMS/NEMS devices with micro and nano features for biomedical applications (BioMEMS/NEMS) using the state of the art microfabrication techniques and biocompatible materials. However, the integration of devices with the biological milieu is still a fundamental issue to be addressed. Devices often fail to operate due to loss of functionality, or generate adverse toxic effects inside the body. The in vitro and in vivo performance of implantable BioMEMS such as biosensors, smart stents, drug delivery systems, and actuation systems are researched extensively to understand the interaction of the BioMEMS devices with physiological environments. BioMEMS developed for drug delivery applications include microneedles, microreservoirs, and micropumps to achieve targeted drug delivery. The biocompatibility of BioMEMS is further enhanced through the application of tissue and smart surface engineering. This involves the application of nanotechnology, which includes the modification of surfaces with polymers or the self-assembly of monolayers of molecules. Thereby, the adverse effects of biofouling can be reduced and the performance of devices can be improved in in vivo and in vitro conditions.

Electrochemical study of nanoporous gold revealing anti-biofouling properties

Nanoporous gold (NPG) has remarkable catalytic activity and biocompatibility and could potentially be used in biomedical devices. Herein, we have assessed the long term effects of biofouling on NPG interface. Nanoporoes (25 nm) in gold electrode are fabricated using a de-alloying treatment resulting in an 18 fold increase in surface area as compared to the planar gold. The effects of biofouling on the planar gold interface were evidenced by the rapid decrease in faradaic current to 55% in just eight minutes of incubation in 2 mg ml−1 of bovine serum albumin (BSA). On the other hand NPG showed barely any decline in the peak current when incubated in a similar biofouling solution. NPG upon incubation in a solution of higher concentration of BSA showed immediate peak current degradation which was subsequently recovered when the electrode was left idle in the biofouling solution. For instance, the peak current regenerated from (60% to 80%) when left idle for 60 minutes in 16 mg ml−1 of BSA solution. The regeneration mechanism indicated that even after long term incubation in the biofouling solution, the accumulated organic layer on its interface is not impervious and allows the diffusion of small analytes molecules. Thereby, NPG could be used in biomedical devices such as biosensor or drug reservoir.

Understanding the adsorption interface of polyelectrolyte coating on redox active nanoparticles using soft particle electrokinetics and its biological activity.

The application of cerium oxide nanoparticles (CNPs) for therapeutic purposes requires a stable dispersion of nanoparticles in a biological environment. The objective of this study is to tailor the properties of polyelectrolyte coated CNPs as a function of molecular weight to achieve a stable and catalytic active dispersion. The coating of CNPs with polyacrylic acid (PAA) has increased the dispersion stability of CNPs and enhanced the catalytic ability. The stability of PAA coating was analyzed using the change in the Gibbs free energy computed by the Langmuir adsorption model. The adsorption isotherms were determined using soft particle electrokinetics which overcomes the challenges presented by other techniques. The change in Gibbs free energy was highest for CNPs coated with PAA of 250 kg/mol indicating the most stable coating. The change in free energy for PAA of 100 kg/mol coated CNPs was 85% lower than the PAA of 250 kg/mol coated CNPs. This significant difference is caused by the strong adsorption of PAA of 100 kg/mol on CNPs. Catalytic activity of PAA-CNPs is assessed by the catalase enzymatic mimetic activity of nanoparticles. The catalase activity was higher for PAA coated CNPs as compared to bare CNPs which indicated preferential adsorption of hydrogen peroxide induced by coating. This indicates that the catalase activity is also affected by the structure of the coating layer.

The change in antioxidant properties of dextran-coated redox active nanoparticles due to synergetic photoreduction-oxidation.

Nanoparticles have proven to be novel material with resourceful applications in the field of nanomedicine. Cerium oxide nanoparticles (CNPs) coated with dextran (Dex-CNPs) have been shown to exhibit anticancer properties which is attributed to the change in oxidation states mediated at the oxygen vacancies on the surface of CNPs. In this study, the extreme sensitivity of Dex-CNPs to visible light is demonstrated using room light with a clear indication of synergetic phenomenon of photoreduction of CNPs in the presence of dextran which undergoes simultaneous oxidation. The phenomenon was further confirmed through a systematic time-based expedited study using a high intensity visible light source. The physiochemical changes of Dex-CNPs such as dispersion stability, pH, surface chemistry, antioxidant property, cytotoxicity and the surrounding microenvironment of Dex-CNPs were significantly altered on exposure to visible light, thereby affecting the biological response. Given the significance of nanoparticles which are widely researched nanomaterials, in different fields of nanotechnology and biomedicine, this study demonstrates the significant changes in physiochemical properties of Dex-CNPs with light. The photoreduction of Dex-CNPs affects its bifunctional applications in cancer therapy and thereby this study puts forward the necessity to preserve and sustain their properties through proper storage.

Picomolar Detection of Hydrogen Peroxide using Enzyme-free Inorganic Nanoparticle-based Sensor

A philosophical shift has occurred in the field of biomedical sciences from treatment of late-stage disease symptoms to early detection and prevention. Ceria nanoparticles (CNPs) have been demonstrated to neutralize free radical chemical species associated with many life-threatening disease states such as cancers and neurodegenerative diseases by undergoing redox changes (Ce3+  ↔ Ce4+). Herein, we investigate the electrochemical response of multi-valent CNPs in presence of hydrogen peroxide and demonstrate an enzyme-free CNP-based biosensor capable of ultra-low (limit of quantitation: 0.1 pM) detection. Several preparations of CNPs with varying Ce3+:Ce4+ are produced and are analyzed by electrochemical methods. We find that an increasing magnitude of response in cyclic voltammetry and chronoamperometry correlates with increasing Ce4+ relative to Ce3+ and utilize this finding in the design of the sensor platform. The sensor retains sensitivity across a range of pH’s and temperatures, wherein enzyme-based sensors will not function, and in blood serum: reflecting selectivity and robustness as a potential implantable biomedical device.

Atmospheric Deposition of Modified Graphene Oxide on Silicon by Evaporation-Assisted Deposition

We present a deposition technique termed evaporation-assisted deposition (EAD). The technique is based on a coupled evaporation-to-condensation transfer process at atmospheric conditions, where graphene oxide (GO) is transferred to a Si wafer via the vapor flux between an evaporating droplet and the Si surface. The EAD process is monitored with visible and infrared cameras. GO deposits on Si are characterized by both Raman spectroscopy and X-ray photoelectron spectroscopy. We find that a scaled energy barrier for the condensate is required for EAD, which corresponds to specific solution–substrate properties that exhibit a minimized free energy barrier at the solid–liquid–vapor interface.