Gold hybrid nanoparticles for targeted phototherapy and cancer imaging

Graduate Field of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
Nanotechnology (Impact Factor: 3.67). 02/2010; 21(10):105105. DOI: 10.1088/0957-4484/21/10/105105
Source: PubMed

ABSTRACT Gold and iron oxide hybrid nanoparticles (HNPs) synthesized by the thermal decomposition technique are bio-functionalized with a single chain antibody, scFv, that binds to the A33 antigen present on colorectal cancer cells. The HNP-scFv conjugates are stable in aqueous solution with a magnetization value of 44 emu g(-1) and exhibit strong optical absorbance at 800 nm. Here we test this material in targeting, imaging and selective thermal killing of colorectal cancer cells. Cellular uptake studies showed that A33-expressing cells take up the A33scFv-conjugated HNPs at a rate five times higher than cells that do not express the A33 antigen. Laser irradiation studies showed that approximately 53% of the A33-expressing cells exposed to targeted HNPs are killed after a six-minute laser treatment at 5.1 W cm(-2) using a 808 nm continuous wave laser diode while < 5% of A33-nonexpressing cells are killed. At a higher intensity, 31.5 W cm(-2), the thermal destruction increases to 99 and 40% for A33-expressing cells and A33 nonexpressing cells, respectively, after 6 min exposure. Flow cytometric analyses of the laser-irradiated A33 antigen-expressing cells show apoptosis-related cell death to be the primary mode of cell death at 5.1 W cm(-2), with increasing necrosis-related cell death at higher laser power. These results suggest that this new class of bio-conjugated hybrid nanoparticles can potentially serve as an effective antigen-targeted photothermal therapeutic agent for cancer treatment as well as a probe for magnetic resonance-based imaging.

1 Follower
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nanocarriers have drastically changed the face of health care by making a mark in diverse arenas of diagnosis, drug delivery, and gene delivery to name a few. The recent feat in nanotechnology has been the birth of nanotheranostics which aims at blending both therapeutic and diagnostic functions within a single nanoscaffold. The field of theranostic nanomedicine is a result of fruitful advances in fields of material science, imaging modalities, formulation development, and molecular biology. Theranostic nanomedicine that was at first developed for enhancing the quality of treatment meted out to cancer patients has now been explored even in atherosclerosis and infections, albeit to a lower extent. The review summarizes various types of nanocarriers that have been explored with one or sometimes multiple imaging modalities for an array of applications ranging from drug delivery and gene delivery to photosensitizing agent delivery for photodynamic therapy. The article also highlights the few but significant developments made in the field of theranostic nanomedicine for atherosclerosis and infections. In conclusion, theranostic nanomedicine is a rapidly growing field. However, there are a few problems that need to be addressed before theranostic nanocarriers carve a niche for themselves in the clinic.
    Journal of Biomedical Nanotechnology 12/2012; 8(6):859-82. DOI:10.1166/jbn.2012.1459 · 7.58 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nanoparticles of varying composition, size, shape, and architecture have been explored for use as photothermal agents in the field of cancer nanomedicine. Among them, gold nanoparticles provide a simple platform for thermal ablation owing to its biocompatibility in vivo. However, the synthesis of such gold nanoparticles exhibiting suitable properties for photothermal activity involves cumbersome routes using toxic chemicals as capping agents, which can cause concerns in vivo. Herein, gold nanoparticles, synthesized using green chemistry routes possessing near-infrared (NIR) absorbance facilitating photothermal therapy, would be a viable alternative. In this study, anisotropic gold nanoparticles were synthesized using an aqueous route with cocoa extract which served both as a reducing and stabilizing agent. The as-prepared gold nanoparticles were subjected to density gradient centrifugation to maximize its NIR absorption in the wavelength range of 800-1000 nm. The particles also showed good biocompatibility when tested in vitro using A431, MDA-MB231, L929, and NIH-3T3 cell lines up to concentrations of 200 μg/mL. Cell death induced in epidermoid carcinoma A431 cells upon irradiation with a femtosecond laser at 800 nm at a low power density of 6 W/cm(2) proved the suitability of green synthesized NIR absorbing anisotropic gold nanoparticles for photothermal ablation of cancer cells. These gold nanoparticles also showed good X-ray contrast when tested using computed tomography (CT), proving their feasibility for use as a contrast agent as well. This is the first report on green synthesized anisotropic and cytocompatible gold nanoparticles without any capping agents and their suitability for photothermal therapy.
    ACS Applied Materials & Interfaces 05/2014; 6(11). DOI:10.1021/am500302t · 5.90 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A novel approach for phototherapy is proposed. The proposed method is based on cell apoptosis according to halting activation of cancer cell membrane receptor by exposure to UV light pulses without any side effect. In the proposed method, gold nanoparticles are directed to cancerous cells by conjugating their surface with specific ligands. UV light is created locally adjacent to cells around the gold nanoparticles. UV light is generated due to nonlinear interaction of visible light with gold nanoparticles because of enhancement in third order nonlinear effects. For example, by using 780 nm laser, 260 nm UV will be generated around the nanoparticle because of third harmonic generation process. As the generated UV is localized around the cell, there will be no side effect for other cells. We have numerically analyzed the proposed method by solving Maxwell's equation considering third order nonlinear susceptibility and dispersion behavior of permittivity by 3D nonlinear finite difference time domain using Newton–Raphson method. Simulation results for different geometries show that UV light will be generated around gold nanoparticle and it is maximum in hot spots where electric field enhancement occurs. Simulation results illustrate that there is neither UV irradiation side effect to healthy cells, nor harmful temperature rise.
    Nano brief reports and reviews 11/2011; 05(06). DOI:10.1142/S1793292010002232 · 1.26 Impact Factor