Hybrid Theranostic Platform for Second Near-IR Window Light Triggered Selective Two-Photon Imaging and Photothermal Killing of Targeted Melanoma Cells

Abstract

Despite advances in the medical field, even in the 21st century cancer is one of the leading causes of death for men and women in the world. Since the second near-infrared (NIR) biological window light between 950 and 1350 nm offers highly efficient tissue penetration, the current article reports the development of hybrid theranostic platform using anti-GD2 antibody attached gold nanoparticle (GNP) conjugated, single-wall carbon nanotube (SWCNT) for second near-IR light triggered selective imaging and efficient photothermal therapy of human melanoma cancer cell. Reported results demonstrate that due to strong plasmon-coupling, two-photon luminescence (TPL) intensity from theranostic GNP attached SWCNT materials is 6 orders of magnitude higher than GNP or SWCNT alone. Experimental and FDTD simulation data indicate that the huge enhancement of TPL intensity is mainly due to strong resonance enhancement coupled with the stronger electric field enhancement. Due to plasmon coupling, the theranostic material serves as a local nanoantennae to enhance the photothermal capability via strong optical energy absorption. Reported data show that theranostic SWCNT can be used for selective two-photon imaging of melanoma UACC903 cell using 1100 nm light. Photothermal killing experiment with 1.0 W/cm(2) 980 nm laser light demonstrates that 100% of melanoma UACC903 cells can be killed using theranostic SWCNT bind melanoma cells after just 8 min of exposure. These results demonstrate that due to plasmon coupling, the theranostic GNP attached SWCNT material serves as a two-photon imaging and photothermal source for cancer cells in biological window II.

Keywords: FDTD simulation; hybrid plasmonic CNT; second biological window; selective photothermal therapy; theranostic platform; two-photon imaging of human melanoma cancer cell.

Figure 1

(A) Scheme showing the synthetic path we have followed for the development of gold nanoparticle attached theranostic SWCNT. (B) TEM data showing how gold nanoparticles are in assembly structure on GNP attached theranostic SWCNT. (C) Extinction spectra shows how the absorption features vary for carboxylic acid conjugated SWCNT, amine functionalized GNP, and theranostic GNP conjugated SWCNT material in water.

Figure 2

(A) Two-photon photoluminescence spectrum from anti-GD2 antibody conjugated SWCNT–GNP theranostic material, anti-GD2 antibody conjugated GNP, and anti-GD2 antibody conjugated SWCNT. NIR light (1100 nm) was used as the excitation source. (B) Plot indicates linear relationship between two-photon photoluminescence intensity at 775 nm from anti-GD2 antibody conjugated SWCNT–GNP theranostic material and the square of intensity of 1100 nm excitation laser power (P_EX). (C) Plot indicates two-photon luminescence at 775 nm from anti-GD2 antibody conjugated SWCNT–GNP remain same even after an hour of exposure with 1100 nm light. (D) Plot reports FDTD simulated electric field enhancement |E|² profiles (arb. unit) for nanoparticle assembly. For our calculation, we have used GNPs particle size as 40 nm, and separation distance between GNPs are kept as 3 nm. (E) Bar plot indicates very good biocompatibility of anti-GD2 antibody conjugated SWCNT–GNP theranostic against melanoma UACC903 cells. Even after 48 h incubation with 80 μg of hybrid material, we have observed about 97% cell viability.

Figure 3

(A) TEM image showing single melanoma UACC903 cell is conjugated with SWCNT–GNP theranostic. (B) Two-photon luminescence image of anti-GD2 antibody conjugated SWCNT–GNP theranostic attached melanoma UACC903 cells. 1100 nm light was used as excitation source.

Figure 4

(A) Bright-field inverted microscopic images of melanoma UACC903 cells after 20 min of exposure by 980 nm light in the absence of anti-GD2 antibody conjugated SWCNT–GNP hybrid theranostic material. Reported data indicate that cancer cells are alive even after 20 min of 980 nm light exposure. (B) Bright-field inverted microscopic images of theranostic SWCNT attached melanoma UACC903 cells after irradiation with 980 nm near-IR biological II window at 1 W/cm² for 6 min. Reported data indicate that most melanoma UACC903 cancer cells are dead after 6 min of photothermal therapy. (C) Bright-field inverted microscopic images of melanoma UACC903 cells after 20 min exposure by 980 nm light in the presence of anti-GD2 antibody conjugated GNP. Reported data indicate that cancer cells are alive even after 20 min of 980 nm light exposure. (D) Plot illustrating the amount of cell viability measured using MTT test for different time intervals of exposure for anti-GD2 antibody conjugated SWCNT, anti-GD2 antibody conjugated GNP, and anti-GD2 antibody conjugated SWCNT–GNP hybrid theranostic material.