Multifunctional plasmonic shell-magnetic core nanoparticles for targeted diagnostics, isolation, and photothermal destruction of tumor cells

Abstract

Cancer is the greatest challenge in human healthcare today. Cancer causes 7.6 million deaths and economic losses of around 1 trillion dollars every year. Early diagnosis and effective treatment of cancer are crucial for saving lives. Driven by these needs, we report the development of a multifunctional plasmonic shell-magnetic core nanotechnology-driven approach for the targeted diagnosis, isolation, and photothermal destruction of cancer cells. Experimental data show that aptamer-conjugated plasmonic/magnetic nanoparticles can be used for targeted imaging and magnetic separation of a particular kind of cell from a mixture of different cancer cells. A targeted photothermal experiment using 670 nm light at 2.5 W/cm(2) for 10 min resulted selective irreparable cellular damage to most of the cancer cells. We also showed that the aptamer-conjugated magnetic/plasmonic nanoparticle-based photothermal destruction of cancer cells is highly selective. We discuss the possible mechanism and operating principle for the targeted imaging, separation, and photothermal destruction using magnetic/plasmonic nanotechnology.

Figure 1

(A) Schematic representation showing the synthesis of S6 aptamer-conjugated multifunctional magnetic core–gold shell nanoparticles. (B) Schematic representation showing the separation of specific cancer cells using S6 aptamer-conjugated plasmonic/magnetic nanoparticles. (C) Schematic representation showing the selective fluorescence imaging and targeted photothermal destruction of specific cancer cells.

Figure 2

(A) Fluorescent images of SK-BR-3 cancer cells after a mixture of LNCaP and SK-BR-3 cells (1:10⁻⁴ ratio) was incubated with Cy3-modified S6 aptamer-conjugated magnetic/plasmonic nanoparticles and separated by a magnet. (B) Bright-field image of the same SK-BR-3 cells after magnetic separation. (C) LNCaP cancer cell fluorescent images after a mixture of LNCaP and SK-BR-3 cells (1:10⁻⁴) was incubated with Cy3-modified S6 aptamer-conjugated magnetic/plasmonic nanoparticles and separated by a magnet. (D) Bright-field image of the same LNCaP cells after magnetic separation. (E) TEM image of SK-BR-3 cells after magnetic separation. The image clearly shows that Cy3-modified S6 aptamer-conjugated magnetic/plasmonic nanoparticles are attached to SK-BR-3 cells. (F) TEM image of LNCaP cells separated by a magnet.

Figure 3

(A) Fluorescent image of SK-BR-3 cancer cells in a mixture of HaCaT and SK-BR-3 cells (1:10⁻⁵ ratio) incubated with Cy3-modified S6 aptamer magnetic/plasmonic nanoparticles and separated by a magnet. (B) Bright-field image of SK-BR-3 cells after magnetic separation. (C) Fluorescent image of HaCaT cells in a mixture of HaCaT and SK-BR-3 cells (1:10⁻⁵ ratio) incubated with Cy3-modified S6 aptamer magnetic/plasmonic nanoparticles and separated by a magnet. (D) Bright-field image of MDA-MB cells after magnetic separation.

Figure 4

(A) Bright-field inverted microscopic images of aptamer-conjugated magnetic/plasmonic nanoparticles attached to SK-BR-3 breast cancer cells after irradiation with 670-nm light at 2.5 W/cm² for 7 minutes followed by staining with trypan blue. (B) Bright-field inverted microscopic images of SK-BR-3 cells alone after irradiation with 670-nm light at 2.5 W/cm² for 10 minutes followed by staining with trypan blue. C) Plot showing cell viability when S-6 aptamer-conjugated magnetic/plasmonic nanoparticles attached to SK-BR-3, MDA-MB, and HaCaT cells were treated using 670-nm light at 2.5 W/cm² for 20 minutes. (D) Plot showing cell viability when S-6 aptamer-conjugated magnetic/plasmonic nanoparticles attached to SK-BR-3 and HaCaT cell mixtures (1:0.01) were treated 670-nm light at 2.5 W/cm² for 20 minutes.

Figure 5

(A) Absorption spectra of SK-BR-3 cancer cells conjugated with magnetic iron oxide (Fe₃O₄) nanoparticles, magnetic core–gold shell nanoparticles, and S6 aptamer-bound magnetic core–gold shell nanoparticles after magnetic separation. (B) TEM image of freshly prepared magnetic nanoparticles. (C) TEM image of freshly prepared plasmonic/magnetic nanoparticles. (D) SEM image of freshly prepared plasmonic/magnetic nanoparticles.