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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

High-resolution darkfield/fluorescence microscopy (top) and two-photon luminescence (TPL) microscopy (bottom) for gold nanoparticle tracking in tumors after leaking through vasculature. 12-nm gold nanospheres were undetectable with TPL imaging in this study, but all nanoparticles were visible darkfield. Gold nanoparticles with smaller size penetrate more deeply into tumor interstitial space. Scale bar, 50 μm. Blue, DAPI; green, CD31; gold nanostars appear yellow in darkfield images and white in TPL images.
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Figure 5: High-resolution darkfield/fluorescence microscopy (top) and two-photon luminescence (TPL) microscopy (bottom) for gold nanoparticle tracking in tumors after leaking through vasculature. 12-nm gold nanospheres were undetectable with TPL imaging in this study, but all nanoparticles were visible darkfield. Gold nanoparticles with smaller size penetrate more deeply into tumor interstitial space. Scale bar, 50 μm. Blue, DAPI; green, CD31; gold nanostars appear yellow in darkfield images and white in TPL images.

Mentions: GNS have extremely strong two-photon luminescence and can be used to monitor nanoparticle distribution at the cellular level without dye labeling. GNS also have a large enough scattering cross-section to allow imaging by darkfield microscopy, in which only the light scattered from indirect illumination of the sample is detected. After CT imaging, tumors were sectioned, immunostained and imaged using two-photon microscopy, fluorescence microscopy, and darkfield microscopy. As shown in Figure 5, both the 30-nm and 60-nm GNS show extremely strong two-photon luminescence. The emitted light spans the visible spectrum, so the nanoparticles appear bright white. It is noteworthy that 12-nm gold nanospheres showed no detectable TPL signal. All three nanoparticle types were visible by darkfield microscopy, but the GNS were much less easily visualized with this modality compared to TPL imaging. Both imaging methods were able to show tissue-level distribution of nanoparticles within the tumor. The 12-nm nanospheres and 30-nm GNS nanoprobes penetrate more deeply into the tissue than 60-nm GNS after leaking through tumor vasculature. The 12-nm nanospheres and 30-nm GNS have a fairly even distribution in tumor tissue, while the larger 60-nm GNS were restricted primarily to the perivascular space.


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)

High-resolution darkfield/fluorescence microscopy (top) and two-photon luminescence (TPL) microscopy (bottom) for gold nanoparticle tracking in tumors after leaking through vasculature. 12-nm gold nanospheres were undetectable with TPL imaging in this study, but all nanoparticles were visible darkfield. Gold nanoparticles with smaller size penetrate more deeply into tumor interstitial space. Scale bar, 50 μm. Blue, DAPI; green, CD31; gold nanostars appear yellow in darkfield images and white in TPL images.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4493533&req=5

Figure 5: High-resolution darkfield/fluorescence microscopy (top) and two-photon luminescence (TPL) microscopy (bottom) for gold nanoparticle tracking in tumors after leaking through vasculature. 12-nm gold nanospheres were undetectable with TPL imaging in this study, but all nanoparticles were visible darkfield. Gold nanoparticles with smaller size penetrate more deeply into tumor interstitial space. Scale bar, 50 μm. Blue, DAPI; green, CD31; gold nanostars appear yellow in darkfield images and white in TPL images.
Mentions: GNS have extremely strong two-photon luminescence and can be used to monitor nanoparticle distribution at the cellular level without dye labeling. GNS also have a large enough scattering cross-section to allow imaging by darkfield microscopy, in which only the light scattered from indirect illumination of the sample is detected. After CT imaging, tumors were sectioned, immunostained and imaged using two-photon microscopy, fluorescence microscopy, and darkfield microscopy. As shown in Figure 5, both the 30-nm and 60-nm GNS show extremely strong two-photon luminescence. The emitted light spans the visible spectrum, so the nanoparticles appear bright white. It is noteworthy that 12-nm gold nanospheres showed no detectable TPL signal. All three nanoparticle types were visible by darkfield microscopy, but the GNS were much less easily visualized with this modality compared to TPL imaging. Both imaging methods were able to show tissue-level distribution of nanoparticles within the tumor. The 12-nm nanospheres and 30-nm GNS nanoprobes penetrate more deeply into the tissue than 60-nm GNS after leaking through tumor vasculature. The 12-nm nanospheres and 30-nm GNS have a fairly even distribution in tumor tissue, while the larger 60-nm GNS were restricted primarily to the perivascular space.

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