MicroCT Imaging and In Vivo Temperature Elevations in Implanted Prostatic Tumors in Laser Photothermal Therapy Using Gold Nanorods

Author(s):  
N. Manuchehrabadi ◽  
A. Attaluri ◽  
H. Cai ◽  
R. Edziah ◽  
E. Lalanne ◽  
...  

In this study, in vivo animal experiments are performed on implanted xenograph prostatic tumors in nude mice to investigate enhanced laser energy absorption in the tumors by an intratumoral injection of gold nanorod solutions. In vivo temperature mapping of the tumors during laser photothermal therapy has shown the feasibility of elevating tumor temperatures higher than 50 °C using only 0.1 ml nanorod solution and a low laser irradiance of 1.6 W/cm2 incident on the tumor surface. The temperature profile suggests that normal tumor tissue still absorbs some amount of the laser energy without nanorod presence; however, the injected nanorods ensure that almost all the laser energy is absorbed and confined to the targeted tumors. The inverse relationship between the temperature elevations and the tumor size implies a relatively uniform spreading of the nanorods to the entire tumor, which is also shown by microcomputed tomography (microCT) imaging analyses. The feasibility of detecting 250 OD gold nanorod solution injected to the tumors is demonstrated via a high resolution microCT imaging system. Compared to other nanostructures, the gold nanorods used in this study do not accumulate surrounding the injection site. The relatively uniform deposition of the nanorods in the tumors observed by the microCT scans can be helpful in future study in simplifying theoretical simulation of temperature elevations in tumors during laser photothermal therapy.

Author(s):  
Navid Manuchehrabadi ◽  
Yonghui Chen ◽  
Alexander LeBrun ◽  
Ronghui Ma ◽  
Liang Zhu

Nanotechnology using gold nanoshells or nanorods is a newly developed hyperthermia approach and has been tested in the past several years in cancer treatment.1–2 Gold nanorods have a diameter of ∼10 nm and an aspect ratio of approximately four. By varying the geometric ratio, the nanostructures can be tuned to have strong absorption and scattering to a specific laser wavelength. Designing an optimal treatment protocol of laser photothermal therapy requires understanding of gold nanorod deposition inside the tumor after injection, its resulted specific absorption rate (SAR) distribution, and the ultimate temperature field in the tumor during the treatment. Recent microCT studies by our group have suggested that the gold nanorod solution injected into PC3 prostatic tumors results in an almost uniform distribution of the gold nanorods in the tumors.3 The Monte Carlo method has been used in the past to determine the heating pattern (SAR) of laser-tissue thermal interaction.4 However, the accuracy of the theoretical simulation of the temperature fields in tumors relies on precise measurements of the optical properties of the tumors with nanorods presence.


Author(s):  
N. Manuchehrabadi ◽  
R. Toughiri ◽  
H. Cai ◽  
L. Zhu ◽  
A. Attaluri ◽  
...  

Gold nanorods can be tuned to a specific laser wavelength and serve as strong laser energy absorbers. Due to the powerful optical absorption, the laser energy is concentrated in an area congregating by nanorods, and then the energy absorbed can be transferred to the surrounding tumor tissue by heat conduction.1–4 Previous studies have shown a wide range of heating parameters with or without temperature measurements. Our previous experiment4 has demonstrated that using only 0.1 cc gold nanorod solution can lead to tumor temperature higher than 50°C when the laser irradiance is only 2 W/cm2. Based on the measured temperature elevation and heating duration, thermal damage to the tumor is highly likely. However, some researchers raised the question whether temperature sensors used in those experimental studies are truly reflecting the temperatures in the tumors. The objective of this study is to measure quantitatively tumor shrinkage after laser irradiation to evaluate efficacy of laser photothermal therapy.


2013 ◽  
Vol 135 (12) ◽  
Author(s):  
Navid Manuchehrabadi ◽  
Yonghui Chen ◽  
Alexander LeBrun ◽  
Ronghui Ma ◽  
Liang Zhu

Accurate simulation of temperature distribution in tumors induced by gold nanorods during laser photothermal therapy relies on precise measurements of thermal, optical, and physiological properties of the tumor with or without nanorods present. In this study, a computational Monte Carlo simulation algorithm is developed to simulate photon propagation in a spherical tumor to calculate laser energy absorption in the tumor and examine the effects of the absorption (μa) and scattering (μs) coefficients of tumors on the generated heating pattern in the tumor. The laser-generated energy deposition distribution is then incorporated into a 3D finite-element model of prostatic tumors embedded in a mouse body to simulate temperature elevations during laser photothermal therapy using gold nanorods. The simulated temperature elevations are compared with measured temperatures in PC3 prostatic tumors in our previous in vivo experimental studies to extract the optical properties of PC3 tumors containing different concentrations of gold nanorods. It has been shown that the total laser energy deposited in the tumor is dominated by μa, while both μa and μs shift the distribution of the energy deposition in the tumor. Three sets of μa and μs are extracted, representing the corresponding optical properties of PC3 tumors containing different concentrations of nanorods to laser irradiance at 808 nm wavelength. With the injection of 0.1 cc of a 250 optical density (OD) nanorod solution, the total laser energy absorption rate is increased by 30% from the case of injecting 0.1 cc of a 50 OD nanorod solution, and by 125% from the control case without nanorod injection. Based on the simulated temperature elevations in the tumor, it is likely that after heating for 15 min, permanent thermal damage occurs in the tumor injected with the 250 OD nanorod solution, while thermal damage to the control tumor and the one injected with the 50 OD nanorod solution may be incomplete.


Nanoscale ◽  
2014 ◽  
Vol 6 (22) ◽  
pp. 13451-13456 ◽  
Author(s):  
Adrian Taruttis ◽  
Neus Lozano ◽  
Antonio Nunes ◽  
Dhifaf A. Jasim ◽  
Nicolas Beziere ◽  
...  

This study describes the simultaneous in vivo optoacousic imaging and siRNA-mediated gene silencing capabilities of a model theranostic vector system between liposomes and gold nanorods.


2017 ◽  
Vol 114 (15) ◽  
pp. E3110-E3118 ◽  
Author(s):  
Moustafa R. K. Ali ◽  
Mohammad Aminur Rahman ◽  
Yue Wu ◽  
Tiegang Han ◽  
Xianghong Peng ◽  
...  

Gold nanorods (AuNRs)-assisted plasmonic photothermal therapy (AuNRs-PPTT) is a promising strategy for combating cancer in which AuNRs absorb near-infrared light and convert it into heat, causing cell death mainly by apoptosis and/or necrosis. Developing a valid PPTT that induces cancer cell apoptosis and avoids necrosis in vivo and exploring its molecular mechanism of action is of great importance. Furthermore, assessment of the long-term fate of the AuNRs after treatment is critical for clinical use. We first optimized the size, surface modification [rifampicin (RF) conjugation], and concentration (2.5 nM) of AuNRs and the PPTT laser power (2 W/cm2) to achieve maximal induction of apoptosis. Second, we studied the potential mechanism of action of AuNRs-PPTT using quantitative proteomic analysis in mouse tumor tissues. Several death pathways were identified, mainly involving apoptosis and cell death by releasing neutrophil extracellular traps (NETs) (NETosis), which were more obvious upon PPTT using RF-conjugated AuNRs (AuNRs@RF) than with polyethylene glycol thiol-conjugated AuNRs. Cytochrome c and p53-related apoptosis mechanisms were identified as contributing to the enhanced effect of PPTT with AuNRs@RF. Furthermore, Pin1 and IL18-related signaling contributed to the observed perturbation of the NETosis pathway by PPTT with AuNRs@RF. Third, we report a 15-month toxicity study that showed no long-term toxicity of AuNRs in vivo. Together, these data demonstrate that our AuNRs-PPTT platform is effective and safe for cancer therapy in mouse models. These findings provide a strong framework for the translation of PPTT to the clinic.


ACS Nano ◽  
2011 ◽  
Vol 5 (2) ◽  
pp. 1086-1094 ◽  
Author(s):  
Boseung Jang ◽  
Jin-Young Park ◽  
Ching-Hsuan Tung ◽  
In-Hoo Kim ◽  
Yongdoo Choi

Author(s):  
N. Manuchehrabadi ◽  
L. Zhu ◽  
A. Attaluri ◽  
H. Cai ◽  
R. Edziah ◽  
...  

In recent years, nanotechnologies have emerged as promising therapies due to their ability to deliver adequate thermal dosage to irregular and/or deep-seated tumors. Gold nanorods can be tuned to a specific laser wavelength and serve as strong laser energy absorbers. Due to the powerful optical absorption, the laser energy is concentrated in an area congregating by nanorods, and then the energy absorbed can be transferred to the surrounding tumor tissue by heat conduction.1–4 Currently, there are wide variation ranges of treatment protocols using photothermal therapy. A systematic approach is lacking to analyze temperature elevation history in tumors during heating to design an optimized combination of laser parameters to maximize thermal damage to tumors.


Author(s):  
Seungsoo Kim ◽  
Yun-Sheng Chen ◽  
Geoffrey P. Luke ◽  
Mohammad Mehrmohammadi ◽  
Jason R. Cook ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document