Article

Gold hybrid nanoparticles for targeted phototherapy and cancer imaging

Graduate Field of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
Nanotechnology (Impact Factor: 3.82). 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.

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    • "The aforementioned optical, magnetic and drug delivery characteristics make Janus particles very interesting candidates for biomedical applications, but detailed data on their cytotoxicity on human cells are missing. So far, experiments assessing the viability of cells after only short exposure (24 and 48 h) to Au@Fe 3 O 4 particles were done using MTT/ WST1 measurements [13] [14]. Nevertheless , it is known that metal nanoparticles can influence these assay systems [9] [19]. "
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    ABSTRACT: The physical properties of asymmetric Janus particles are highly promising for future biomedical applications. However, only a few data is available on their biological impact on human cells. We investigated the biological impact of different Au@Fe3O4 Janus particle formulations in vitro to analyse specific uptake modalities and their potential cytotoxic effects on human cells of the blood regarding intravenous injection. We demonstrate that Au@Fe3O4 Janus particles exhibit a similar or even better biocompatibility compared to the well-studied spherical iron oxide nanoparticles. The impact of Janus particles on cells depends mainly on three factors. (1) Surface functionalization: NH2-functionalization of the Au or iron oxide domain induces a pronounced reduction of cell viability in contrast to non-functionalized variants which is caused by the damage of intracellular membranes. (2) The nature of the metal oxide component, greatly affects cell viability, as shown by a comparison with Au@MnO Janus particles. (3) The overall surface charge and the size of nanoparticles have a higher impact on internalization and cellular metabolism than the Janus character per se. Interestingly, Janus particle associated DNA damage is independent of the effects on the cellular ATP level. However, not only the structure and functionalization of the Janus particle surface determines the particle's adhesion and intracellular fate, but also the constitution of the cell surface as shown by different modification experiments. The multifactorial in vitro approach presented in this study demonstrated the high capability of the Janus particles. Especially Au@Fe3O4 Janus particles bear great potential for applications in vivo.
    Preview · Article · May 2014 · Biomaterials
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    Full-text · Article · Jan 2014
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    • "The aforementioned optical, magnetic and drug delivery characteristics make Janus particles very interesting candidates for biomedical applications, but detailed data on their cytotoxicity on human cells are missing. So far, experiments assessing the viability of cells after only short exposure (24 and 48 h) to Au@Fe 3 O 4 particles were done using MTT/ WST1 measurements [13] [14]. Nevertheless , it is known that metal nanoparticles can influence these assay systems [9] [19]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The physical properties of asymmetric Janus particles are highly promising for future biomedical applications. However, only a few data is available on their biological impact on human cells. We investigated the biological impact of different Au@Fe3O4 Janus particle formulations in vitro to analyse specific uptake modalities and their potential cytotoxic effects on human cells of the blood regarding intravenous injection. We demonstrate that Au@Fe3O4 Janus particles exhibit a similar or even better biocompatibility compared to the well-studied spherical iron oxide nanoparticles. The impact of Janus particles on cells depends mainly on three factors. (1) Surface functionalization: NH2-functionalization of the Au or iron oxide domain induces a pronounced reduction of cell viability in contrast to non-functionalized variants which is caused by the damage of intracellular membranes. (2) The nature of the metal oxide component, greatly affects cell viability, as shown by a comparison with Au@MnO Janus particles. (3) The overall surface charge and the size of nanoparticles have a higher impact on internalization and cellular metabolism than the Janus character per se. Interestingly, Janus particle associated DNA damage is independent of the effects on the cellular ATP level. However, not only the structure and functionalization of the Janus particle surface determines the particle's adhesion and intracellular fate, but also the constitution of the cell surface as shown by different modification experiments. The multifactorial in vitro approach presented in this study demonstrated the high capability of the Janus particles. Especially Au@Fe3O4 Janus particles bear great potential for applications in vivo.
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