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Papers by Christine Tarapacki

The effectiveness of PEG coated gold nanorod and laser thermal therapy (AuNR+L) depends on gold n... more The effectiveness of PEG coated gold nanorod and laser thermal therapy (AuNR+L) depends on gold nanoparticle delivery. The application of ultrasound and microbubbles (USMB) has been shown to enhance drug delivery across cell membranes. This study investigated the effect of the combined treatment of ultrasound and microbubbles with PEG coated gold nanorod thermal therapy on cancer cells. Cells in suspension were exposed to combinations of AuNR, laser, and USMB. Following the treatment, cell viability was assessed with propidium iodide marker and flow cytometry, and with colony assays. Cell death significantly increased when USMB was combined with AuNR+L during laser treatment compared to either treatment on its own, whereas, in the absence of AuNR, NIR laser light had a protective effect on cells exposed to USMB. Generally, USMB induced an additive therapeutic effect on cell viability when combined with AuNR+L.

PLOS ONE

The use of ultrasound-stimulated microbubble therapy has successfully been used to target tumor v... more The use of ultrasound-stimulated microbubble therapy has successfully been used to target tumor vasculature and enhance the effects of radiation therapy in tumor xenografts in mice. Here, we further investigate this treatment using larger, more clinically relevant tumor models. New Zealand white rabbits bearing prostate tumor (PC3) xenografts received a single treatment of either ultrasound-stimulated microbubbles (USMB), ionizing radiation (XRT; 8Gy), or a combination of both treatments (USMB+XRT). Treatment outcome was evaluated 24 hours after treatment using histopathology, immunolabeling, 3D Doppler ultrasound and photoacoustic imaging. A second cohort of rabbits received multiple treatments over a period of three weeks, where USMB treatments were delivered twice weekly with daily XRT treatments to deliver a fractionated 2Gy dose five days per week. A significant decrease in vascular function, observed through immunolabeling of vascular endothelial cells, was observed in tumors receiving the combined treatment (USMB+XRT) compared to control and single treatment groups. This was associated with an increase in cell death as observed through in situ end labeling (ISEL), a decrease in vascular index measured by Power Doppler imaging, and a decrease in oxygen saturation. In rabbits undergoing the long-term fractionated combined treatment, a significant growth delay was observed after 1 week and a significant reduction in tumor size was observed after 3 weeks with combined therapy. Results demonstrated an enhancement of radiation effect and superior anti-tumor effect of the combination of USMB+XRT compared to the single treatments alone. Tumor growth was maximally inhibited with fractionated radiotherapy combined with the ultrasound-stimulated microbubble-based therapy.

reported that radiation can induce changes in CT texture features in tumor during RT delivery for... more reported that radiation can induce changes in CT texture features in tumor during RT delivery for lung cancer and such changes can be potentially used to assess RT response. In this work, we investigate if radiation-induced changes in CT Hounsfield unit (HU) histogram feature in the periphery of lung tumor can be correlated to tumor response. Materials/Methods: Diagnostic-quality CTs acquired with an in-room CT (CT-on-Rails) during daily CT-guided RT for 10 lung cancer patients, including 2 cases from an external source, were analyzed. For each case, all CT sets were acquired with the same protocol. Lesion for each case was contoured using a thresholding algorithm set at a minimum of À100 HUs to exclude lung tissue. This contour was expanded by 1 cm to form the periphery, then cloned and translated to the contralateral lung as control. To obtain the peripheral and contralateral contours, a second threshold region was set to only obtain regions between À1024 and À100 HU within the expanded (peripheral) and translated (contralateral) contours. Various HU histogram characteristics were extracted from both regions and were correlated with tumor response as characterized by good response (e.g., local recurrence-free survival above 3 years) and poor response (e.g., local recurrence within 1 year or high SUV uptake in follow-up PET). Results: After normalization to account for changes in the volume of the tumor lesion, the HU histograms of different RT fractions in the tumor periphery in patients with good RT response showed a shift toward normal lung histograms as determined using the contralateral lung. These changes could be characterized with 2 general trends: (1) positive shift in peripheral histogram values by at least 20 HU, resulting in overlap with the normal lung; and (2) decrease in the percentage of volume within the shoulder region above the peak. Poorly responding patients showed minimal change in the peripheral HU histograms during RT. Despite decrease in lesion sizes for most patients, overall shape and characteristics of normalized tumor HU histograms remained consistent throughout the course of treatment. No/minimal change was seen in the contralateral lung. Conclusion: Radiation can induce changes in CT HU histogram features in the tumor periphery during RT delivery for lung cancer patients who have good responses to RT. During RT delivery, HU histograms in the periphery of lung tumors appear to exhibit a treatment-related shift toward histograms more characteristic of normal lungs. Such a shift was observed even for a case with no shift in the HU histograms in the tumor. This shift does not occur in patients who are responding poorly to RT. These radiationinduced changes in HU histogram features in tumor periphery may be used to assess radiation response during RT delivery.

Background: The application of ultrasound and microbubbles at therapeutic conditions has been sho... more Background: The application of ultrasound and microbubbles at therapeutic conditions has been shown to improve delivery of molecules, cause vasoconstriction, modulate blood flow and induce a vascular shut down in in vivo cancerous tissues. The underlying mechanism has been associated with the interaction of ultrasonically-induced microbubble oscillation and cavitation with the blood vessel wall. In this study, the effect of ultrasound and microbubbles on blood flow and vascular architecture was studied using a fertilized chicken egg CAM (chorioallantoic membrane) model. Methods: CAM at day 12 of incubation (Hamburger-Hamilton stage 38-40) were exposed to ultrasound at varying acoustic pressures (160, 240 and 320 kPa peak negative pressure) in the presence of Definity microbubbles and 70 kDa FITC dextran fluorescent molecules. A volume of 50 μL Definity microbubbles were injected into a large anterior vein of the CAM prior to ultrasound exposure. The ultrasound treatment sequence consisted of 5 s exposure at 500 kHz frequency, 8 cycles and 1 kHz pulse repetition frequency with 5 s off for a total exposure of 2 minutes. Fluorescent videos and images of the CAM vasculature were acquired using intravital microscopy prior, during and following the ultrasound exposure. Perfusion was quantified by measuring the length of capillaries in a region of interest using Adobe Illustrator. Results and Discussion: The vascular bioeffects induced by USMB increased with acoustic peak negative pressure. At 160 kPa, no visible differences were observed compared to the control. At 240 kPa, a transient decrease in perfusion with subsequent recovery within 15 minutes was observed, whereas at 320 kPa, the fluorescent images showed an irreversible vascular damage. The study indicates that a potential mechanism for the transient decrease in perfusion may be related to blood coagulation. The results suggest that ultrasound and microbubbles can induce reversible and irreversible vascular changes depending on the ultrasound exposure pressure.

Radiotherapy and Oncology

Oncoscience, 2016

Acoustically stimulated microbubbles have been demonstrated to perturb endothelial cells of the v... more Acoustically stimulated microbubbles have been demonstrated to perturb endothelial cells of the vasculature resulting in biological effects. In the present study, vascular and tumor response to ultrasound-stimulated microbubble and radiation treatment was investigated in vivo to identify effects on the blood vessel endothelium. Mice bearing breast cancer tumors (MDA-MB-231) were exposed to ultrasound after intravenous injection of microbubbles at different concentrations, and radiation at different doses (0, 2, and 8 Gy). Mice were sacrificed 12 and 24 hours after treatment for histopathological analysis. Tumor growth delay was assessed for up to 28 days after treatment. The results demonstrated additive antitumor and antivascular effects when ultrasound stimulated microbubbles were combined with radiation. Results indicated tumor cell apoptosis, vascular leakage, a decrease in tumor vasculature, a delay in tumor growth and an overall tumor disruption. When coupled with radiation, u...

Ultrasonics, 2013

Gold nanorods (GNRs) are being exploited for their absorption properties to improve thermal thera... more Gold nanorods (GNRs) are being exploited for their absorption properties to improve thermal therapy. However, a key challenge is delivering sufficient concentration of GNRs to induce a therapeutic effect. In this study, ultrasound and microbubbles (USMBs) were used to enhance intracellular uptake of GNRs. AML-5 cells in suspension (0.6 mL) were exposed to ultrasound (1.3 and 1.7 MPa peak negative pressure) and definity microbubbles (1.7% v/v) for 1 min at varying GNR concentrations (0-2.5×10(11) per mL). Following ultrasound-microbubble treatment, cells were centrifuged twice and treated with an 810 nm laser at an average fluence rate of 3.6 W/cm(2) for 5 min. In addition, cells were incubated with GNRs for 12 h prior to laser treatment. Following the treatment, cell viability (V(PI)) was assessed using propidium iodide (PI) and flow cytometry. Cell viability decreased by ∼4-folds with the combined treatment of USMB+GNR+Laser (V(PI)=17%) compared to cells incubated with GNR+Laser (V(PI)=68%). This effect depended on ultrasound pressure and GNR concentration. Higher cell death was achieved at higher GNR concentration and 1.3 MPa peak negative pressure. Cell viability decreased from 92% to 29% with increasing GNR concentration from 1×10(11) to 1.5×10(11) GNR/mL. In addition, higher temperatures were observed using a thermal camera with the combined treatment (USMB+GNR+Laser) of 59±1°C compared to 54±0.9°C for cells incubated with GNRs. The combined treatment of ultrasound-microbubble and gold nanorod laser induced thermal-therapy improved treatment response of in vitro cells.

The Canadian Journal of Chemical Engineering

Journal of Medical Imaging and Radiation Sciences, 2016

Journal of Medical Imaging and Radiation Sciences, 2016

Ultrasonics, 2015

Gold nanorod (AuNR) laser therapy (LT) is a non-invasive method of increasing the temperature of ... more Gold nanorod (AuNR) laser therapy (LT) is a non-invasive method of increasing the temperature of a target tissue using near infrared light. In this study, the effects of ultrasound and microbubbles (USMB) with AuNR and LT were investigated on cell viability. MDA-MB-231 cells in suspension were treated with three different treatment combinations of AuNR, LT and USMB (Pneg=0.6 or 1.0 MPa): (1) AuNR with USMB followed by LT, (2) AuNR and LT followed by USMB, and (3) USMB followed by AuNR and LT. Cells were also exposed to USMB and LT without AuNR. The USMB conditions were: 500 kHz frequency, 16 cycles, 1kHz pulse repetition frequency for 1 min in the presence of Definity microbubbles (1.7% v/v). AuNR and LT conditions were: mPEG coated AuNR at 3×10(11) np/mL and 1.9 W/cm(2) for 3 min. Following the treatment, cell viability was assessed using propidium iodide (PI) fluorescent marker and flow cytometry (VPI), and colony assay (VCA). Cell viabilities were compared using a non-parametric ...

Ultrasonics, 2013

Gold nanorods (GNR) in laser-induced thermal therapy can significantly increase light absorption,... more Gold nanorods (GNR) in laser-induced thermal therapy can significantly increase light absorption, leading to a local temperature increase and causing irreversible cell damage. One of the key challenges in using GNR as a thermal therapy agent is to deliver a concentration of GNR to generate sufficient heat and cause cell death. In this study, ultrasound and microbubble induced sonoporation is used to enhance intracellular uptake of GNR and improve the therapeutic outcome of laserinduced thermal therapy. Acute myeloid leukemia (AML) cells in suspension (0.6 mL) were treated with ultrasound and microbubbles (USMB) at 1 MHz frequency, 16 microseconds pulse duration, 1 kHz pulse repetition frequency, 1 minute insonation time, varying acoustic pressures (0, 1.26 and 1.73 MPa) and 10 µL Definity microbubble agent with and without GNR (12 nm x 48 nm) at varying concentration (1.0x10 10 to 2.5x10 11 GNR/mL). The GNR were manufactured through wet chemical synthesis process and measured using Transmission Electron Microscopy (TEM) and Atomic Absorption Spectroscopy (AAS) for size and concentration respectively. Following ultrasound and microbubble treatment, cells were centrifuged to remove excess gold nanorods and treated in suspension with an 810 nm laser (Diomed 60 NIR) at 4 W for 5 minutes. A thermal camera (FLIR Thermovision A40) was positioned to monitor the sample temperature throughout laser treatment and cell viability was assessed using flow cytometry with propidium iodide. Cell viability of 18±2% was achieved with GNR+USMB (1.26 MPa) compared to 72±3% with GNR alone (12 hour incubation) and 99±0.2% with USMB (1.26 MPa) alone. With increasing GNR concentration during ultrasound and microbubble treatment, laser induced sample temperature increased and consequently cell viability decreased. Cell viability decreased from 92±1% at 1.0x10 11 GNR/mL to 29±5% at 1.5x10 11 GNR/mL concentration with corresponding maximum temperatures of 50°C and 54°C, respectively. The combined treatment of ultrasound-microbubble and gold nanorod laser induced thermal-therapy showed a synergistic enhancement of cell death in vitro. This study shows promise for an enhanced therapeutic effect with the combined treatment in vivo.

The effectiveness of PEG coated gold nanorod and laser thermal therapy (AuNR+L) depends on gold n... more The effectiveness of PEG coated gold nanorod and laser thermal therapy (AuNR+L) depends on gold nanoparticle delivery. The application of ultrasound and microbubbles (USMB) has been shown to enhance drug delivery across cell membranes. This study investigated the effect of the combined treatment of ultrasound and microbubbles with PEG coated gold nanorod thermal therapy on cancer cells. Cells in suspension were exposed to combinations of AuNR, laser, and USMB. Following the treatment, cell viability was assessed with propidium iodide marker and flow cytometry, and with colony assays. Cell death significantly increased when USMB was combined with AuNR+L during laser treatment compared to either treatment on its own, whereas, in the absence of AuNR, NIR laser light had a protective effect on cells exposed to USMB. Generally, USMB induced an additive therapeutic effect on cell viability when combined with AuNR+L.

PLOS ONE

The use of ultrasound-stimulated microbubble therapy has successfully been used to target tumor v... more The use of ultrasound-stimulated microbubble therapy has successfully been used to target tumor vasculature and enhance the effects of radiation therapy in tumor xenografts in mice. Here, we further investigate this treatment using larger, more clinically relevant tumor models. New Zealand white rabbits bearing prostate tumor (PC3) xenografts received a single treatment of either ultrasound-stimulated microbubbles (USMB), ionizing radiation (XRT; 8Gy), or a combination of both treatments (USMB+XRT). Treatment outcome was evaluated 24 hours after treatment using histopathology, immunolabeling, 3D Doppler ultrasound and photoacoustic imaging. A second cohort of rabbits received multiple treatments over a period of three weeks, where USMB treatments were delivered twice weekly with daily XRT treatments to deliver a fractionated 2Gy dose five days per week. A significant decrease in vascular function, observed through immunolabeling of vascular endothelial cells, was observed in tumors receiving the combined treatment (USMB+XRT) compared to control and single treatment groups. This was associated with an increase in cell death as observed through in situ end labeling (ISEL), a decrease in vascular index measured by Power Doppler imaging, and a decrease in oxygen saturation. In rabbits undergoing the long-term fractionated combined treatment, a significant growth delay was observed after 1 week and a significant reduction in tumor size was observed after 3 weeks with combined therapy. Results demonstrated an enhancement of radiation effect and superior anti-tumor effect of the combination of USMB+XRT compared to the single treatments alone. Tumor growth was maximally inhibited with fractionated radiotherapy combined with the ultrasound-stimulated microbubble-based therapy.

reported that radiation can induce changes in CT texture features in tumor during RT delivery for... more reported that radiation can induce changes in CT texture features in tumor during RT delivery for lung cancer and such changes can be potentially used to assess RT response. In this work, we investigate if radiation-induced changes in CT Hounsfield unit (HU) histogram feature in the periphery of lung tumor can be correlated to tumor response. Materials/Methods: Diagnostic-quality CTs acquired with an in-room CT (CT-on-Rails) during daily CT-guided RT for 10 lung cancer patients, including 2 cases from an external source, were analyzed. For each case, all CT sets were acquired with the same protocol. Lesion for each case was contoured using a thresholding algorithm set at a minimum of À100 HUs to exclude lung tissue. This contour was expanded by 1 cm to form the periphery, then cloned and translated to the contralateral lung as control. To obtain the peripheral and contralateral contours, a second threshold region was set to only obtain regions between À1024 and À100 HU within the expanded (peripheral) and translated (contralateral) contours. Various HU histogram characteristics were extracted from both regions and were correlated with tumor response as characterized by good response (e.g., local recurrence-free survival above 3 years) and poor response (e.g., local recurrence within 1 year or high SUV uptake in follow-up PET). Results: After normalization to account for changes in the volume of the tumor lesion, the HU histograms of different RT fractions in the tumor periphery in patients with good RT response showed a shift toward normal lung histograms as determined using the contralateral lung. These changes could be characterized with 2 general trends: (1) positive shift in peripheral histogram values by at least 20 HU, resulting in overlap with the normal lung; and (2) decrease in the percentage of volume within the shoulder region above the peak. Poorly responding patients showed minimal change in the peripheral HU histograms during RT. Despite decrease in lesion sizes for most patients, overall shape and characteristics of normalized tumor HU histograms remained consistent throughout the course of treatment. No/minimal change was seen in the contralateral lung. Conclusion: Radiation can induce changes in CT HU histogram features in the tumor periphery during RT delivery for lung cancer patients who have good responses to RT. During RT delivery, HU histograms in the periphery of lung tumors appear to exhibit a treatment-related shift toward histograms more characteristic of normal lungs. Such a shift was observed even for a case with no shift in the HU histograms in the tumor. This shift does not occur in patients who are responding poorly to RT. These radiationinduced changes in HU histogram features in tumor periphery may be used to assess radiation response during RT delivery.

Background: The application of ultrasound and microbubbles at therapeutic conditions has been sho... more Background: The application of ultrasound and microbubbles at therapeutic conditions has been shown to improve delivery of molecules, cause vasoconstriction, modulate blood flow and induce a vascular shut down in in vivo cancerous tissues. The underlying mechanism has been associated with the interaction of ultrasonically-induced microbubble oscillation and cavitation with the blood vessel wall. In this study, the effect of ultrasound and microbubbles on blood flow and vascular architecture was studied using a fertilized chicken egg CAM (chorioallantoic membrane) model. Methods: CAM at day 12 of incubation (Hamburger-Hamilton stage 38-40) were exposed to ultrasound at varying acoustic pressures (160, 240 and 320 kPa peak negative pressure) in the presence of Definity microbubbles and 70 kDa FITC dextran fluorescent molecules. A volume of 50 μL Definity microbubbles were injected into a large anterior vein of the CAM prior to ultrasound exposure. The ultrasound treatment sequence consisted of 5 s exposure at 500 kHz frequency, 8 cycles and 1 kHz pulse repetition frequency with 5 s off for a total exposure of 2 minutes. Fluorescent videos and images of the CAM vasculature were acquired using intravital microscopy prior, during and following the ultrasound exposure. Perfusion was quantified by measuring the length of capillaries in a region of interest using Adobe Illustrator. Results and Discussion: The vascular bioeffects induced by USMB increased with acoustic peak negative pressure. At 160 kPa, no visible differences were observed compared to the control. At 240 kPa, a transient decrease in perfusion with subsequent recovery within 15 minutes was observed, whereas at 320 kPa, the fluorescent images showed an irreversible vascular damage. The study indicates that a potential mechanism for the transient decrease in perfusion may be related to blood coagulation. The results suggest that ultrasound and microbubbles can induce reversible and irreversible vascular changes depending on the ultrasound exposure pressure.

Radiotherapy and Oncology

Oncoscience, 2016

Acoustically stimulated microbubbles have been demonstrated to perturb endothelial cells of the v... more Acoustically stimulated microbubbles have been demonstrated to perturb endothelial cells of the vasculature resulting in biological effects. In the present study, vascular and tumor response to ultrasound-stimulated microbubble and radiation treatment was investigated in vivo to identify effects on the blood vessel endothelium. Mice bearing breast cancer tumors (MDA-MB-231) were exposed to ultrasound after intravenous injection of microbubbles at different concentrations, and radiation at different doses (0, 2, and 8 Gy). Mice were sacrificed 12 and 24 hours after treatment for histopathological analysis. Tumor growth delay was assessed for up to 28 days after treatment. The results demonstrated additive antitumor and antivascular effects when ultrasound stimulated microbubbles were combined with radiation. Results indicated tumor cell apoptosis, vascular leakage, a decrease in tumor vasculature, a delay in tumor growth and an overall tumor disruption. When coupled with radiation, u...

Ultrasonics, 2013

Gold nanorods (GNRs) are being exploited for their absorption properties to improve thermal thera... more Gold nanorods (GNRs) are being exploited for their absorption properties to improve thermal therapy. However, a key challenge is delivering sufficient concentration of GNRs to induce a therapeutic effect. In this study, ultrasound and microbubbles (USMBs) were used to enhance intracellular uptake of GNRs. AML-5 cells in suspension (0.6 mL) were exposed to ultrasound (1.3 and 1.7 MPa peak negative pressure) and definity microbubbles (1.7% v/v) for 1 min at varying GNR concentrations (0-2.5×10(11) per mL). Following ultrasound-microbubble treatment, cells were centrifuged twice and treated with an 810 nm laser at an average fluence rate of 3.6 W/cm(2) for 5 min. In addition, cells were incubated with GNRs for 12 h prior to laser treatment. Following the treatment, cell viability (V(PI)) was assessed using propidium iodide (PI) and flow cytometry. Cell viability decreased by ∼4-folds with the combined treatment of USMB+GNR+Laser (V(PI)=17%) compared to cells incubated with GNR+Laser (V(PI)=68%). This effect depended on ultrasound pressure and GNR concentration. Higher cell death was achieved at higher GNR concentration and 1.3 MPa peak negative pressure. Cell viability decreased from 92% to 29% with increasing GNR concentration from 1×10(11) to 1.5×10(11) GNR/mL. In addition, higher temperatures were observed using a thermal camera with the combined treatment (USMB+GNR+Laser) of 59±1°C compared to 54±0.9°C for cells incubated with GNRs. The combined treatment of ultrasound-microbubble and gold nanorod laser induced thermal-therapy improved treatment response of in vitro cells.

The Canadian Journal of Chemical Engineering

Journal of Medical Imaging and Radiation Sciences, 2016

Journal of Medical Imaging and Radiation Sciences, 2016

Ultrasonics, 2015

Gold nanorod (AuNR) laser therapy (LT) is a non-invasive method of increasing the temperature of ... more Gold nanorod (AuNR) laser therapy (LT) is a non-invasive method of increasing the temperature of a target tissue using near infrared light. In this study, the effects of ultrasound and microbubbles (USMB) with AuNR and LT were investigated on cell viability. MDA-MB-231 cells in suspension were treated with three different treatment combinations of AuNR, LT and USMB (Pneg=0.6 or 1.0 MPa): (1) AuNR with USMB followed by LT, (2) AuNR and LT followed by USMB, and (3) USMB followed by AuNR and LT. Cells were also exposed to USMB and LT without AuNR. The USMB conditions were: 500 kHz frequency, 16 cycles, 1kHz pulse repetition frequency for 1 min in the presence of Definity microbubbles (1.7% v/v). AuNR and LT conditions were: mPEG coated AuNR at 3×10(11) np/mL and 1.9 W/cm(2) for 3 min. Following the treatment, cell viability was assessed using propidium iodide (PI) fluorescent marker and flow cytometry (VPI), and colony assay (VCA). Cell viabilities were compared using a non-parametric ...

Ultrasonics, 2013

Gold nanorods (GNR) in laser-induced thermal therapy can significantly increase light absorption,... more Gold nanorods (GNR) in laser-induced thermal therapy can significantly increase light absorption, leading to a local temperature increase and causing irreversible cell damage. One of the key challenges in using GNR as a thermal therapy agent is to deliver a concentration of GNR to generate sufficient heat and cause cell death. In this study, ultrasound and microbubble induced sonoporation is used to enhance intracellular uptake of GNR and improve the therapeutic outcome of laserinduced thermal therapy. Acute myeloid leukemia (AML) cells in suspension (0.6 mL) were treated with ultrasound and microbubbles (USMB) at 1 MHz frequency, 16 microseconds pulse duration, 1 kHz pulse repetition frequency, 1 minute insonation time, varying acoustic pressures (0, 1.26 and 1.73 MPa) and 10 µL Definity microbubble agent with and without GNR (12 nm x 48 nm) at varying concentration (1.0x10 10 to 2.5x10 11 GNR/mL). The GNR were manufactured through wet chemical synthesis process and measured using Transmission Electron Microscopy (TEM) and Atomic Absorption Spectroscopy (AAS) for size and concentration respectively. Following ultrasound and microbubble treatment, cells were centrifuged to remove excess gold nanorods and treated in suspension with an 810 nm laser (Diomed 60 NIR) at 4 W for 5 minutes. A thermal camera (FLIR Thermovision A40) was positioned to monitor the sample temperature throughout laser treatment and cell viability was assessed using flow cytometry with propidium iodide. Cell viability of 18±2% was achieved with GNR+USMB (1.26 MPa) compared to 72±3% with GNR alone (12 hour incubation) and 99±0.2% with USMB (1.26 MPa) alone. With increasing GNR concentration during ultrasound and microbubble treatment, laser induced sample temperature increased and consequently cell viability decreased. Cell viability decreased from 92±1% at 1.0x10 11 GNR/mL to 29±5% at 1.5x10 11 GNR/mL concentration with corresponding maximum temperatures of 50°C and 54°C, respectively. The combined treatment of ultrasound-microbubble and gold nanorod laser induced thermal-therapy showed a synergistic enhancement of cell death in vitro. This study shows promise for an enhanced therapeutic effect with the combined treatment in vivo.