TY - JOUR
T1 - In vitro and in vivo mapping of drug release after laser ablation thermal therapy with doxorubicin-loaded hollow gold nanoshells using fluorescence and photoacoustic imaging
AU - Lee, Hannah J.
AU - Liu, Yang
AU - Zhao, Jun
AU - Zhou, Min
AU - Bouchard, Richard R.
AU - Mitcham, Trevor
AU - Wallace, Michael
AU - Stafford, R. Jason
AU - Li, Chun
AU - Gupta, Sanjay
AU - Melancon, Marites P.
N1 - Funding Information:
The authors thank Joe Munch in MD Anderson's Department of Scientific Publications for editing the manuscript. This work was supported in part by a grant from the John S. Dunn Foundation (to C.L.) and by the National Institutes of Health through MD Anderson's Cancer Center Support Grant CA016672 for the small animal imaging and veterinary pathology core facilities.
PY - 2013
Y1 - 2013
N2 - Doxorubicin-loaded hollow gold nanoshells (Dox@PEG-HAuNS) increase the efficacy of photothermal ablation (PTA) not only by mediating efficient PTA but also through chemotherapy, and therefore have potential utility for local anticancer therapy. However, in vivo real-time monitoring of Dox release and temperature achieved during the laser ablation technique has not been previously demonstrated before. In this study, we used fluorescence optical imaging to map the release of Dox from Dox@PEG-HAuNS and photoacoustic imaging to monitor the tumor temperature achieved during near-infrared laser-induced photothermal heating in vitro and in vivo. In vitro, treatment with a 3-W laser was sufficient to initiate the release of Dox from Dox@PEG-HAuNS (1:3:1 wt/wt, 1.32 × 1012 particles/mL). Laser powers of 3 and 6 W achieved ablative temperatures of more than 50 C. In 4T1 tumor-bearing nude mice that received intratumoral or intravenous injections of Dox@PEG-HAuNS, fluorescence optical imaging (emission wavelength = 600 nm, excitation wavelength = 500 nm) revealed that the fluorescence intensity in surface laser-treated tumors 24 h after treatment was significantly higher than that in untreated tumors (p = 0.015 for intratumoral, p = 0.008 for intravenous). Similar results were obtained using an interstitial laser to irradiate tumors following the intravenous injection of Dox@PEG-HAuNS (p = 0.002 at t = 24 h). Photoacoustic imaging (acquisition wavelength = 800 nm) revealed that laser treatment caused a substantial increase in tumor temperature, from 37 C to ablative temperatures of more than 50 C. Ex vivo analysis revealed that the fluorescence intensity of laser-treated tumors was twice as high as that of untreated tumors (p = 0.009). Histological analysis confirmed that intratumoral injection of Dox@PEG-HAuNS and laser treatment caused significantly more tumor necrosis compared to tumors that were not treated with laser (p < 0.001). On the basis of these findings, we conclude that fluorescence optical imaging and photoacoustic imaging are promising approaches to assessing Dox release and monitoring temperature, respectively, after Dox@PEG-HAuNS-mediated thermal ablation therapy.
AB - Doxorubicin-loaded hollow gold nanoshells (Dox@PEG-HAuNS) increase the efficacy of photothermal ablation (PTA) not only by mediating efficient PTA but also through chemotherapy, and therefore have potential utility for local anticancer therapy. However, in vivo real-time monitoring of Dox release and temperature achieved during the laser ablation technique has not been previously demonstrated before. In this study, we used fluorescence optical imaging to map the release of Dox from Dox@PEG-HAuNS and photoacoustic imaging to monitor the tumor temperature achieved during near-infrared laser-induced photothermal heating in vitro and in vivo. In vitro, treatment with a 3-W laser was sufficient to initiate the release of Dox from Dox@PEG-HAuNS (1:3:1 wt/wt, 1.32 × 1012 particles/mL). Laser powers of 3 and 6 W achieved ablative temperatures of more than 50 C. In 4T1 tumor-bearing nude mice that received intratumoral or intravenous injections of Dox@PEG-HAuNS, fluorescence optical imaging (emission wavelength = 600 nm, excitation wavelength = 500 nm) revealed that the fluorescence intensity in surface laser-treated tumors 24 h after treatment was significantly higher than that in untreated tumors (p = 0.015 for intratumoral, p = 0.008 for intravenous). Similar results were obtained using an interstitial laser to irradiate tumors following the intravenous injection of Dox@PEG-HAuNS (p = 0.002 at t = 24 h). Photoacoustic imaging (acquisition wavelength = 800 nm) revealed that laser treatment caused a substantial increase in tumor temperature, from 37 C to ablative temperatures of more than 50 C. Ex vivo analysis revealed that the fluorescence intensity of laser-treated tumors was twice as high as that of untreated tumors (p = 0.009). Histological analysis confirmed that intratumoral injection of Dox@PEG-HAuNS and laser treatment caused significantly more tumor necrosis compared to tumors that were not treated with laser (p < 0.001). On the basis of these findings, we conclude that fluorescence optical imaging and photoacoustic imaging are promising approaches to assessing Dox release and monitoring temperature, respectively, after Dox@PEG-HAuNS-mediated thermal ablation therapy.
KW - Magnetic resonance temperature imaging
KW - Molecular imaging
KW - Near-infrared optical imaging
KW - Photoacoustic imaging
KW - Targeted hollow gold nanoshells
UR - http://www.scopus.com/inward/record.url?scp=84883493786&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84883493786&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2013.07.020
DO - 10.1016/j.jconrel.2013.07.020
M3 - Article
C2 - 23920038
AN - SCOPUS:84883493786
SN - 0168-3659
VL - 172
SP - 152
EP - 158
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 1
ER -