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.

  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: Poly(ethylene glycol)-b-poly(N-vinylcaprolactam) (PEG-b-PNVCL) copolymers are prepared from a PEG macro-chain transfer agent in DMF at 65 °C via reversible addition–fragmentation chain transfer (RAFT) polymerization. The well-defined PEG114-b-PNVCL237 copolymer with a cloud point temperature of 39 °C is used for the formation of a thermo-responsive polymer corona on the surface of gold nanorods (GNRs) via a “grafting-to” approach. Thermo-responsiveness and thermo-dependent optical properties of the as-obtained GNR@PEG-b-PNVCL nanoparticles are studied with dynamic light scattering and UV/vis spectroscopy techniques. Near infrared (NIR)-induced heating of GNR@PEG-b-PNVCL is also explored in aqueous suspension under NIR laser irradiation (802 nm, up to 250 mW). The potential of these GNR@PEG-b-PNVCL nanoparticles to be used as smart drug delivery systems (DDS) is then studied. A hydrophilic drug model, Rhodamine® B, is used to assess the guest loading capacity, and triggered release behaviours are then evaluated under conventional external heating or internal heating induced by remote NIR irradiation. Cytotoxicity evaluation of the GNR@PEG-b-PNVCL against the fibroblast-like L929 cell line is carried out via the MTS assay in order to confirm the improved biocompatibility of the GNRs after polymer coating. These thermo-responsive GNR@PEG-b-PNVCL nanoparticles are promising DDS that combine the chemotherapeutic and phototherapeutic functions.
    12/2013; 5(3). DOI:10.1039/C3PY01057K
  • [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