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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

Maximum intensity projection CT images of hind leg primary sarcomas at 30 minutes, 24 hours, and 72 hours after gold nanoparticle injection (12-nm nanospheres, 30-nm and 60-nm GNS). Gold concentrations are shown in green (windowed from 2 to 10 mg/ml), while other tissues are shown in gray scale (windowed from -100 to 5000 HU). Gold is primarily visualized in the blood vessels immediately after injection and in the tissues in the delayed scans.
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Figure 3: Maximum intensity projection CT images of hind leg primary sarcomas at 30 minutes, 24 hours, and 72 hours after gold nanoparticle injection (12-nm nanospheres, 30-nm and 60-nm GNS). Gold concentrations are shown in green (windowed from 2 to 10 mg/ml), while other tissues are shown in gray scale (windowed from -100 to 5000 HU). Gold is primarily visualized in the blood vessels immediately after injection and in the tissues in the delayed scans.

Mentions: In order to further investigate gold nanoparticles' dynamic biodistribution and demonstrate real-time monitoring of intratumoral accumulation, we performed dual-energy CT imaging on mice with primary sarcomas 30 minutes, 24 hours, and 72 hours after gold nanoparticles injection. Mice with primary sarcomas are immunocompetent and may more accurately reflect the tumor microenvironment and response to therapy of human tumors compared to xenograft models.44-46 The longitudinal dual-energy CT imaging showed gold nanoparticle distribution at various time points (Figure 3). The CT images at 30 minutes clearly show gold nanoparticles localized to blood vessels. It appears that the majority of blood vessels in the tumor region were located on the outside of the tumor, so perfusion to the core of the tumor may be limited. At the 24-hour and 72-hour time points, there was nanoparticle accumulation in the tumors. Concentrations of gold in the blood, tumors, and other organs calculated from each dual-energy CT scan are shown in the Supplementary Figure S1. These results are consistent with the results obtained with radiolabelled GNS, showing significant RES accumulation and tumor uptake, as well as decreasing concentrations of gold within the blood over time. The most notable difference between these two biodistribution studies is that the concentration of gold in the tumor relative to the liver and spleen was much higher in the CT study than in the radiolabeled study. This is most likely due to the much higher dose of gold injected for the CT study. The RES might be saturated with a high injection dose, which would give the nanoparticles a longer circulation time. It is also possible that the tumor nanoparticle uptake differs between the primary tumor and xenograft mouse models. Blood residence time for each nanoparticle type was approximated using the measured gold concentrations in the blood at 0, 24, and 72 hours post-injection. 12-nm nanospheres had a blood half-life of approximately 26 hours; 30-nm GNS had a half-life of 33 hours; and 60-nm GNS had a half-life of 27 hours, which is consistent with residence times we have seen in previous gold nanoparticle studies.39 These CT results also show a comparison of the concentrations of gold within the tumor rim and tumor core. In all three cases, there was high gold concentration in the tumor rim and negligible gold concentration in the tumor core. CT slices through the tumors demonstrate this heterogeneous intratumoral distribution (Figure 4). The gold concentration at the rim is much higher than that in the center and is not evenly distributed around the tumor rim. The low concentration at the center may reflect poor perfusion in the tumor core. This is supported by the H&E images (Supplementary Figure S2), which show tumor necrosis at the core, but viable tumor near the margins. Additionally, the 12-nm nanospheres showed much more skin accumulation around the tumor site than the larger GNS. Images of the gross primary sarcomas before extraction are shown in Supplementary Figure S3. They show that the surface of the sarcoma is black in color due to high GNS accumulation, consistent with the CT cross-sectional images. There is also a clearly visible color boundary between tumor and normal muscle due to differential GNS uptake, which indicates that GNS could potentially be used as an intraoperative imaging contrast agent during cancer surgery.


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)

Maximum intensity projection CT images of hind leg primary sarcomas at 30 minutes, 24 hours, and 72 hours after gold nanoparticle injection (12-nm nanospheres, 30-nm and 60-nm GNS). Gold concentrations are shown in green (windowed from 2 to 10 mg/ml), while other tissues are shown in gray scale (windowed from -100 to 5000 HU). Gold is primarily visualized in the blood vessels immediately after injection and in the tissues in the delayed scans.
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Related In: Results  -  Collection

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Figure 3: Maximum intensity projection CT images of hind leg primary sarcomas at 30 minutes, 24 hours, and 72 hours after gold nanoparticle injection (12-nm nanospheres, 30-nm and 60-nm GNS). Gold concentrations are shown in green (windowed from 2 to 10 mg/ml), while other tissues are shown in gray scale (windowed from -100 to 5000 HU). Gold is primarily visualized in the blood vessels immediately after injection and in the tissues in the delayed scans.
Mentions: In order to further investigate gold nanoparticles' dynamic biodistribution and demonstrate real-time monitoring of intratumoral accumulation, we performed dual-energy CT imaging on mice with primary sarcomas 30 minutes, 24 hours, and 72 hours after gold nanoparticles injection. Mice with primary sarcomas are immunocompetent and may more accurately reflect the tumor microenvironment and response to therapy of human tumors compared to xenograft models.44-46 The longitudinal dual-energy CT imaging showed gold nanoparticle distribution at various time points (Figure 3). The CT images at 30 minutes clearly show gold nanoparticles localized to blood vessels. It appears that the majority of blood vessels in the tumor region were located on the outside of the tumor, so perfusion to the core of the tumor may be limited. At the 24-hour and 72-hour time points, there was nanoparticle accumulation in the tumors. Concentrations of gold in the blood, tumors, and other organs calculated from each dual-energy CT scan are shown in the Supplementary Figure S1. These results are consistent with the results obtained with radiolabelled GNS, showing significant RES accumulation and tumor uptake, as well as decreasing concentrations of gold within the blood over time. The most notable difference between these two biodistribution studies is that the concentration of gold in the tumor relative to the liver and spleen was much higher in the CT study than in the radiolabeled study. This is most likely due to the much higher dose of gold injected for the CT study. The RES might be saturated with a high injection dose, which would give the nanoparticles a longer circulation time. It is also possible that the tumor nanoparticle uptake differs between the primary tumor and xenograft mouse models. Blood residence time for each nanoparticle type was approximated using the measured gold concentrations in the blood at 0, 24, and 72 hours post-injection. 12-nm nanospheres had a blood half-life of approximately 26 hours; 30-nm GNS had a half-life of 33 hours; and 60-nm GNS had a half-life of 27 hours, which is consistent with residence times we have seen in previous gold nanoparticle studies.39 These CT results also show a comparison of the concentrations of gold within the tumor rim and tumor core. In all three cases, there was high gold concentration in the tumor rim and negligible gold concentration in the tumor core. CT slices through the tumors demonstrate this heterogeneous intratumoral distribution (Figure 4). The gold concentration at the rim is much higher than that in the center and is not evenly distributed around the tumor rim. The low concentration at the center may reflect poor perfusion in the tumor core. This is supported by the H&E images (Supplementary Figure S2), which show tumor necrosis at the core, but viable tumor near the margins. Additionally, the 12-nm nanospheres showed much more skin accumulation around the tumor site than the larger GNS. Images of the gross primary sarcomas before extraction are shown in Supplementary Figure S3. They show that the surface of the sarcoma is black in color due to high GNS accumulation, consistent with the CT cross-sectional images. There is also a clearly visible color boundary between tumor and normal muscle due to differential GNS uptake, which indicates that GNS could potentially be used as an intraoperative imaging contrast agent during cancer surgery.

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