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A Plasmonic Gold Nanostar Theranostic Probe for In Vivo Tumor Imaging and Photothermal Therapy.

Liu Y, Ashton JR, Moding EJ, Yuan H, Register JK, Fales AM, Choi J, Whitley MJ, Zhao X, Qi Y, Ma Y, Vaidyanathan G, Zalutsky MR, Kirsch DG, Badea CT, Vo-Dinh T - Theranostics (2015)

Bottom Line: Nanomedicine has attracted increasing attention in recent years, because it offers great promise to provide personalized diagnostics and therapy with improved treatment efficacy and specificity.We also characterized the performance of the GNS nanoprobe for in vitro photothermal heating and in vivo photothermal ablation of primary sarcomas in mice.In vivo photothermal therapy with a near-infrared (NIR) laser under the maximum permissible exposure (MPE) led to ablation of aggressive tumors containing GNS, but had no effect in the absence of GNS.

View Article: PubMed Central - PubMed

Affiliation: 1. Fitzpatrick Institute for Photonics, Duke University, Durham, NC, 27708, United States ; 2. Department of Biomedical Engineering, Duke University, Durham, NC, 27708, United States ; 3. Department of Chemistry, Duke University, Durham, NC, 27708, United States.

ABSTRACT
Nanomedicine has attracted increasing attention in recent years, because it offers great promise to provide personalized diagnostics and therapy with improved treatment efficacy and specificity. In this study, we developed a gold nanostar (GNS) probe for multi-modality theranostics including surface-enhanced Raman scattering (SERS) detection, x-ray computed tomography (CT), two-photon luminescence (TPL) imaging, and photothermal therapy (PTT). We performed radiolabeling, as well as CT and optical imaging, to investigate the GNS probe's biodistribution and intratumoral uptake at both macroscopic and microscopic scales. We also characterized the performance of the GNS nanoprobe for in vitro photothermal heating and in vivo photothermal ablation of primary sarcomas in mice. The results showed that 30-nm GNS have higher tumor uptake, as well as deeper penetration into tumor interstitial space compared to 60-nm GNS. In addition, we found that a higher injection dose of GNS can increase the percentage of tumor uptake. We also demonstrated the GNS probe's superior photothermal conversion efficiency with a highly concentrated heating effect due to a tip-enhanced plasmonic effect. In vivo photothermal therapy with a near-infrared (NIR) laser under the maximum permissible exposure (MPE) led to ablation of aggressive tumors containing GNS, but had no effect in the absence of GNS. This multifunctional GNS probe has the potential to be used for in vivo biosensing, preoperative CT imaging, intraoperative detection with optical methods (SERS and TPL), as well as image-guided photothermal therapy.

No MeSH data available.


Related in: MedlinePlus

In vitro photothermal heating evaluation. (A) Repetitive photothermal heating (0.2 nM 30-nm GNS solution) with 0.8 W/cm2 laser (980 nm wavelength) on at 0, 25, and 50 minutes and laser off at 10, 35, and 60 minutes. (B) Temperature profile for different GNS concentrations with 0.8 W/cm2 laser intensity. (C) Temperature profile for 0.2 nM GNS with different laser intensities. (D) Temperature profile for 12-nm gold nanospheres (5 nM) and water with 0.8 W/cm2 laser intensity. No photothermal enhancement was observed for 12-nm gold nanospheres compared to water. (E) Temperature profile of 30-nm GNS, 60-nm GNS, and gold nanoshells for photothermal conversion efficiency calculations. (F) Calculated photothermal conversion efficiency for GNS nanoprobes and gold nanoshells as a comparison (n=3 for each group).
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Figure 7: In vitro photothermal heating evaluation. (A) Repetitive photothermal heating (0.2 nM 30-nm GNS solution) with 0.8 W/cm2 laser (980 nm wavelength) on at 0, 25, and 50 minutes and laser off at 10, 35, and 60 minutes. (B) Temperature profile for different GNS concentrations with 0.8 W/cm2 laser intensity. (C) Temperature profile for 0.2 nM GNS with different laser intensities. (D) Temperature profile for 12-nm gold nanospheres (5 nM) and water with 0.8 W/cm2 laser intensity. No photothermal enhancement was observed for 12-nm gold nanospheres compared to water. (E) Temperature profile of 30-nm GNS, 60-nm GNS, and gold nanoshells for photothermal conversion efficiency calculations. (F) Calculated photothermal conversion efficiency for GNS nanoprobes and gold nanoshells as a comparison (n=3 for each group).

Mentions: In addition to its use as an imaging and tumor detection agent, the developed multifunctional GNS probe can also be used for photothermal therapy. Because the 30-nm GNS accumulate more in tumors and have deeper tissue penetration than the 60-nm GNS, we selected 30-nm GNS to investigate in vivo photothermal therapy. The 30-nm GNS probe was first tested with in vitro experiments, the results of which are shown in Figure 7. After three repetitive laser irradiations (0.8 W/cm2), there was no decrease in the photon-to-heat conversion (Figure 7A). Figures 7B and 7C demonstrate that equilibrium temperature varies with GNS concentration and laser power. Water (no GNS) increased from room temperature to ~31 °C after extended laser irradiation, while the 0.5 nM GNS solution increased to ~42 °C upon continuous irradiation. Equilibrium was reached after about 10 minutes of irradiation at all GNS concentrations. This equilibrium temperature depends strongly on laser power, as shown in Figure 7C. Although increasing laser power clearly led to higher final temperatures, the 0.7 W/cm2 laser power was chosen for in vivo studies in order to minimize non-target tissue damage and keep exposure levels under the recommended maximum permissible exposure (MPE). We also performed calculations to investigate how efficiently GNS can facilitate photothermal therapy (Supplementary Figure S4). The results suggest that GNS have a high photothermal conversion efficiency and that the temperature at the GNS surface could be high enough to vaporize surrounding water molecules. This finding is supported by the presence of significant condensation on the sides of the cuvette after even short periods of irradiation (with bulk solution temperature < 40 °C).


A Plasmonic Gold Nanostar Theranostic Probe for In Vivo Tumor Imaging and Photothermal Therapy.

Liu Y, Ashton JR, Moding EJ, Yuan H, Register JK, Fales AM, Choi J, Whitley MJ, Zhao X, Qi Y, Ma Y, Vaidyanathan G, Zalutsky MR, Kirsch DG, Badea CT, Vo-Dinh T - Theranostics (2015)

In vitro photothermal heating evaluation. (A) Repetitive photothermal heating (0.2 nM 30-nm GNS solution) with 0.8 W/cm2 laser (980 nm wavelength) on at 0, 25, and 50 minutes and laser off at 10, 35, and 60 minutes. (B) Temperature profile for different GNS concentrations with 0.8 W/cm2 laser intensity. (C) Temperature profile for 0.2 nM GNS with different laser intensities. (D) Temperature profile for 12-nm gold nanospheres (5 nM) and water with 0.8 W/cm2 laser intensity. No photothermal enhancement was observed for 12-nm gold nanospheres compared to water. (E) Temperature profile of 30-nm GNS, 60-nm GNS, and gold nanoshells for photothermal conversion efficiency calculations. (F) Calculated photothermal conversion efficiency for GNS nanoprobes and gold nanoshells as a comparison (n=3 for each group).
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Related In: Results  -  Collection

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Figure 7: In vitro photothermal heating evaluation. (A) Repetitive photothermal heating (0.2 nM 30-nm GNS solution) with 0.8 W/cm2 laser (980 nm wavelength) on at 0, 25, and 50 minutes and laser off at 10, 35, and 60 minutes. (B) Temperature profile for different GNS concentrations with 0.8 W/cm2 laser intensity. (C) Temperature profile for 0.2 nM GNS with different laser intensities. (D) Temperature profile for 12-nm gold nanospheres (5 nM) and water with 0.8 W/cm2 laser intensity. No photothermal enhancement was observed for 12-nm gold nanospheres compared to water. (E) Temperature profile of 30-nm GNS, 60-nm GNS, and gold nanoshells for photothermal conversion efficiency calculations. (F) Calculated photothermal conversion efficiency for GNS nanoprobes and gold nanoshells as a comparison (n=3 for each group).
Mentions: In addition to its use as an imaging and tumor detection agent, the developed multifunctional GNS probe can also be used for photothermal therapy. Because the 30-nm GNS accumulate more in tumors and have deeper tissue penetration than the 60-nm GNS, we selected 30-nm GNS to investigate in vivo photothermal therapy. The 30-nm GNS probe was first tested with in vitro experiments, the results of which are shown in Figure 7. After three repetitive laser irradiations (0.8 W/cm2), there was no decrease in the photon-to-heat conversion (Figure 7A). Figures 7B and 7C demonstrate that equilibrium temperature varies with GNS concentration and laser power. Water (no GNS) increased from room temperature to ~31 °C after extended laser irradiation, while the 0.5 nM GNS solution increased to ~42 °C upon continuous irradiation. Equilibrium was reached after about 10 minutes of irradiation at all GNS concentrations. This equilibrium temperature depends strongly on laser power, as shown in Figure 7C. Although increasing laser power clearly led to higher final temperatures, the 0.7 W/cm2 laser power was chosen for in vivo studies in order to minimize non-target tissue damage and keep exposure levels under the recommended maximum permissible exposure (MPE). We also performed calculations to investigate how efficiently GNS can facilitate photothermal therapy (Supplementary Figure S4). The results suggest that GNS have a high photothermal conversion efficiency and that the temperature at the GNS surface could be high enough to vaporize surrounding water molecules. This finding is supported by the presence of significant condensation on the sides of the cuvette after even short periods of irradiation (with bulk solution temperature < 40 °C).

Bottom Line: Nanomedicine has attracted increasing attention in recent years, because it offers great promise to provide personalized diagnostics and therapy with improved treatment efficacy and specificity.We also characterized the performance of the GNS nanoprobe for in vitro photothermal heating and in vivo photothermal ablation of primary sarcomas in mice.In vivo photothermal therapy with a near-infrared (NIR) laser under the maximum permissible exposure (MPE) led to ablation of aggressive tumors containing GNS, but had no effect in the absence of GNS.

View Article: PubMed Central - PubMed

Affiliation: 1. Fitzpatrick Institute for Photonics, Duke University, Durham, NC, 27708, United States ; 2. Department of Biomedical Engineering, Duke University, Durham, NC, 27708, United States ; 3. Department of Chemistry, Duke University, Durham, NC, 27708, United States.

ABSTRACT
Nanomedicine has attracted increasing attention in recent years, because it offers great promise to provide personalized diagnostics and therapy with improved treatment efficacy and specificity. In this study, we developed a gold nanostar (GNS) probe for multi-modality theranostics including surface-enhanced Raman scattering (SERS) detection, x-ray computed tomography (CT), two-photon luminescence (TPL) imaging, and photothermal therapy (PTT). We performed radiolabeling, as well as CT and optical imaging, to investigate the GNS probe's biodistribution and intratumoral uptake at both macroscopic and microscopic scales. We also characterized the performance of the GNS nanoprobe for in vitro photothermal heating and in vivo photothermal ablation of primary sarcomas in mice. The results showed that 30-nm GNS have higher tumor uptake, as well as deeper penetration into tumor interstitial space compared to 60-nm GNS. In addition, we found that a higher injection dose of GNS can increase the percentage of tumor uptake. We also demonstrated the GNS probe's superior photothermal conversion efficiency with a highly concentrated heating effect due to a tip-enhanced plasmonic effect. In vivo photothermal therapy with a near-infrared (NIR) laser under the maximum permissible exposure (MPE) led to ablation of aggressive tumors containing GNS, but had no effect in the absence of GNS. This multifunctional GNS probe has the potential to be used for in vivo biosensing, preoperative CT imaging, intraoperative detection with optical methods (SERS and TPL), as well as image-guided photothermal therapy.

No MeSH data available.


Related in: MedlinePlus