Srinivas Sridhar

Nanoporous inorganic membranes or coatings for sustained drug delivery in implantable devices

The characteristics of nanoporous inorganic coatings on implants or on implantable devices are reviewed. The commonly used nanoporous materials, such as aluminum oxide (Al(2)O(3)), titanium oxide (TiO(2)) and porous silicon are highlighted with illustrative examples. The critical issues for sustained release systems are examined and the elution profiles of nanoporous coatings are discussed. The available data shows that these systems can be used effectively for sustained release applications. They satisfy the basic biocompatibility tests, meet the requirements of drug loading and sustained release profiles extending to several weeks and also are compatible with current implant technologies. Nanoporous inorganic coatings are well suited to provide improved efficacy and integration of implants in a variety of therapeutic situations.

Negative Refraction and Left-Handed Electromagnetism in Microwave Photonic Crystals

We demonstrate the negative refraction of microwaves in a metallic photonic crystal prism. The spectral response of the photonic crystal prism, which manifests both positive and negative refraction, is in complete agreement with band-structure calculations and numerical simulations. The validity of Snells law with a negative refractive index is confirmed experimentally and theoretically. The negative refraction observed corresponds to left-handed electromagnetism that arises due to the dispersion characteristics of waves in a periodic medium. This mechanism for negative refraction is different from that in metamaterials.

Super-resolution imaging using a three-dimensional metamaterials nanolens

Super-resolution imaging beyond Abbe’s diffraction limit can be achieved by utilizing an optical medium or “metamaterial” that can either amplify or transport the decaying near-field evanescent waves that carry subwavelength features of objects. Earlier approaches at optical frequencies mostly utilized the amplification of evanescent waves in thin metallic films or metal-dielectric multilayers, but were restricted to very small thicknesses (⪡λ, wavelength) and accordingly short object-image distances, due to losses in the material. Here, we present an experimental demonstration of super-resolution imaging by a low-loss three-dimensional metamaterial nanolens consisting of aligned gold nanowires embedded in a porous alumina matrix. This composite medium possesses strongly anisotropic optical properties with negative permittivity in the nanowire axis direction, which enables the transport of both far-field and near-field components with low-loss over significant distances (>6λ), and over a broad spectral ra...

Novel technique to measure the microwave response of high Tc superconductors between 4.2 and 200 K

We have devised and implemented a novel technique that has the required sensitivity to enable measurements of the complex surface impedance (Zs) of high Tc superconducting materials between 4.2 K and at least 200 K. The essential ideal is to employ a superconducting high‐Q cavity resonator operated at an ambient temperature of 4.2 K. The sample, mounted on a sapphire rod, is placed inside the cavity at a high magnetic field location, and is thermally insulated from the cavity walls, enabling external control of the sample temperature between 4.2 and 200 K. The cavity characteristics are dominated by the sample properties—the Pb walls maintained at 4.2 K contribute negligibly. Measurement of the cavity Q and resonant frequency enables the measurement of Zs as a function of the sample temperature. The technique is applicable to both bulk and thin‐film materials. We have used this technique with success to measure Zs, at 9.58 GHz, for bulk Y1Ba2Cu3Oy and La1.85Sr0.15CuO4 over a temperature range from 4.2 to ...

Technique for measuring the frequency‐dependent complex dielectric constants of liquids up to 20 GHz

A technique for the measurement of the frequency‐dependent complex dielectric constant e=e’−je‘ of liquids applicable to frequencies up to at least 20 GHz is described. The technique utilizes a coaxial probe dipped into the liquid. The reflection coefficient of the probe was measured using a network analyzer between 45 MHz and 20 GHz. A new de‐imbedding procedure for eliminating the connector and coax mismatches is described, during which the impedance Z(e) of the probe end was determined. The dielectric constant e was determined from Z(e) by modeling the coax–liquid interface as a capacitance. The de‐imbedding procedure, which utilizes three calibrations, directly eliminates the (unknown) fringe‐field impedance. Radiation effects were minimized by using narrow (0.047‐in.) semirigid coax. The technique yields accurate results for e’ and e‘ of liquids such as methanol and water over the entire frequency range up to 20 GHz, and can be used to determine the relaxation spectra of liquid and liquidlike samples.

Superlens imaging theory for anisotropic nanostructured metamaterials with broadband all-angle negative refraction

In this Brief Report, we show that such aligned nanowire structures in dielectric matrices constitute a class of indefinite index media with strongly anisotropic optical properties that can be used to achieve broadband all-angle NR AANR and superlens imaging. We show that these anisotropic media will have two surface plasmon resonances SPR: a longitudinal SPR and a transverse SPR. For wavelength larger than that of the longitudinal SPR, these media are negative index metamaterials and can be used for superlens imaging 4,13 in the frequency range from the deep-infrared up to the ultraviolet. NR and superlens imaging are possible due to the anisotropic optical properties. These structures do not need to be periodic. Disordered structures can also be used for NR. Example systems are designed and demonstrated. We consider a metal with Re m0 embedded in an ambient medium with positive a. In the long wavelength limit, one has the Bruggeman’s effective medium theory

Targeted radiotherapy with gold nanoparticles: current status and future perspectives

Radiation therapy (RT) is the treatment of cancer and other diseases with ionizing radiation. The ultimate goal of RT is to destroy all the disease cells while sparing healthy tissue. Towards this goal, RT has advanced significantly over the past few decades in part due to new technologies including: multileaf collimator-assisted modulation of radiation beams, improved computer-assisted inverse treatment planning, image guidance, robotics with more precision, better motion management strategies, stereotactic treatments and hypofractionation. With recent advances in nanotechnology, targeted RT with gold nanoparticles (GNPs) is actively being investigated as a means to further increase the RT therapeutic ratio. In this review, we summarize the current status of research and development towards the use of GNPs to enhance RT. We highlight the promising emerging modalities for targeted RT with GNPs and the corresponding preclinical evidence supporting such promise towards potential clinical translation. Future prospects and perspectives are discussed.

In vitro radiosensitization by gold nanoparticles during continuous low-dose-rate gamma irradiation with I-125 brachytherapy seeds

UNLABELLED This communication reports the first experimental evidence of gold nanoparticle (AuNP) radiosensitization during continuous low-dose-rate (LDR) gamma irradiation with low-energy brachytherapy sources. HeLa cell cultures incubated with and without AuNP were irradiated with an I-125 seed plaque designed to produce a relatively homogeneous dose distribution in the plane of the cell culture slide. Four sets of irradiation experiments were conducted at low-dose rates ranging from 2.1 to 4.5cGy/h. Residual γH2AX was measured 24h after irradiation and used to compare radiation damage to the cells with and without AuNP. The data demonstrate that the biological effect when irradiating in the presence of 0.2mg/ml concentration of AuNP is about 70%-130% greater than without AuNP. Meanwhile, without radiation, the AuNP showed minimal effect on the cancer cells. These findings provide in vitro evidence that AuNP may be employed as radiosensitizers during continuous LDR brachytherapy. FROM THE CLINICAL EDITOR In this basic science paper, the application of gold nanoparticles as radiosensitizing agents for low dose rate gamma radiation therapy is discussed, demonstrating efficacy in cell culture models.

Nanoparticle Mediated Tumor Vascular Disruption: A Novel Strategy in Radiation Therapy.

More than 50% of all cancer patients receive radiation therapy. The clinical delivery of curative radiation dose is strictly restricted by the proximal healthy tissues. We propose a dual-targeting strategy using vessel-targeted-radiosensitizing gold nanoparticles and conformal-image guided radiation therapy to specifically amplify damage in the tumor neoendothelium. The resulting tumor vascular disruption substantially improved the therapeutic outcome and subsidized the radiation/nanoparticle toxicity, extending its utility to intransigent or nonresectable tumors that barely respond to standard therapies.

PARP inhibitors: A new era of targeted therapy.

Personalized medicine seeks to utilize targeted therapies with increased selectivity and efficacy in preselected patient cohorts. One such molecularly targeted therapy is enabled by inhibiting the enzyme poly(ADP-ribose) polymerase (PARP) by small molecule inhibitors in tumors which have a defect in the homologous DNA recombination pathway, most characteristically due to BRCA mutations. Olaparib, a highly potent PARP inhibitor, has recently been the approved for ovarian cancer therapy by the FDA and European commission in patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer with BRCA1 or BRCA2 mutations. Currently, clinical trials with several PARP inhibitors are being conducted to assess the toxicities, the efficacies and the benefit of the drugs as monotherapies or combined with radiation or other chemotherapeutic agents, in ovarian, breast, prostate, rectal, lung, pancreatic, peritoneal, head and neck, brain, squamous cell carcinomas and sarcomas, to list a few. In this review, our focus is to outline the emerging molecular mechanisms, preclinical evidence and clinical applications of PARP inhibitors especially in nonBRCA cancers, and review the combination strategies compatible with PARP inhibitor therapy.