Enhancement of gold nanorods-assisted photothermal treatment on cancer with laser power in stepwise modulation.

Photothermal therapy (PTT) is a minimally invasive or noninvasive method by destructing cancer cells through selective thermal decomposition. However, a long period of laser irradiation to achieve coagulative necrosis often causes unfavorable thermal damage to the surrounding healthy tissue. The current study aims to evaluate the feasibility of temporal power modulation to improve the treatment efficacy of gold nanorods-assisted PTT against tumor tissue. A total of 25 µg/ml of PEGylated gold nanorods (PEG-GNR) was used as an absorbing agent during 1064 nm laser irradiation for PTT. Temperature monitoring was conducted on the aqueous solution of PEG-GNR for dosimetry comparison. For in vivo tests, CT-26 tumor-bearing murine models with PEG-GNR injected were treated with three irradiation conditions: 3 W/cm2 for 90 s, 1.5 W/cm2 for 180 s, and 3 W/cm2 for 60 s followed by 1.5 W/cm2 for 60 s (modulated). Ten days after the treatments, histology analysis was performed to assess the extent of coagulation necrosis in the treated tissues. The temporal power modulation maintained the tissue temperature of around 50°C for a longer period during the irradiation. Histology analysis confirmed that the modulated group entailed a larger coagulative necrosis area with less thermal damage to the peripheral tissue, compared to the other irradiation conditions. Therefore, the power-modulated PTT could improve treatment efficacy with reduced injury by maintaining the constant tissue temperature. Further studies will examine the feasibility of the proposed technique in large animal models in terms of acute and chronic tissue responses and treatment margin for clinical translations.

Kim Y ，Kim H ，Kang HW 《-》

Thermal effects and biological response of breast and pancreatic cancer cells undergoing gold nanorod-assisted photothermal therapy.

To increase the therapeutic efficacy of nanoparticle (NP)-assisted photothermal therapy (PTT) and allow for a transition toward the clinical setting, it is pivotal to characterize the thermal effect induced in cancer cells and correlate it with the cell biological response, namely cell viability and cell death pathways. This study quantitatively evaluated the effects of gold nanorod (GNR)-assisted near-infrared (NIR) PTT on two different cancer cell lines, the 4T1 triple-negative breast cancer cells and the Pan02 pancreatic cancer cells. The interaction between nanomaterials and biological matrices was investigated in terms of GNR internalization and effect on cell viability at different GNR concentrations. GNR-mediated PTT was executed on both cell lines, at the same treatment settings to allow a straightforward comparison, and real-time monitored through thermographic imaging. A thermal analysis based on various parameters (i.e., maximum absolute temperature, maximum temperature change, temperature variation profile, area under the time-temperature change curve, effective thermal enhancement (ETE), and time constants) was performed to evaluate the treatment thermal outcome. While GNR treatment and NIR laser irradiation alone did not cause cell toxicity in the selected settings, their combination induced a significant reduction of cell viability in both cell lines. At the optimal experimental condition (i.e., 6 μg/mL of GNRs and 4.5 W/cm2 laser power density), GNR-assisted PTT reduced the cell viability of 4T1 and Pan02 cells by 94% and 87% and it was associated with maximum temperature changes of 25 °C and 29 °C (i.e., ∼1.8-fold increase compared to the laser-only condition), maximum absolute temperatures of 55 °C and 54 °C, and ETE values of 78% and 81%, for 4T1 and Pan02 cells, correspondingly. Also, the increase in the GNR concentration led to a decrease in the time constants, denoting faster heating kinetics upon irradiation. Furthermore, the thermal analysis parameters were correlated with the extent of cell death. Twelve hours after NIR exposure, GNR-assisted PTT was found to mainly trigger secondary apoptosis in both cell lines. The proposed study provides relevant insights into the relationship between temperature history and biological responses in the context of PTT. The findings contribute to the development of a universal methodology for evaluating thermal sensitivity upon NP-assisted PTT on different cell types and lay the groundwork for future translational studies.

Bianchi L ，Baroni S ，Paroni G ，Violatto MB ，Moscatiello GY ，Panini N ，Russo L ，Fiordaliso F ，Colombo L ，Diomede L ，Saccomandi P ，Bigini P ... -  《-》

A numerical study to investigate the effects of tumour position on the treatment of bladder cancer in mice using gold nanorods assisted photothermal ablation.

Gold nanorods assisted photothermal therapy (GNR-PTT) is a new cancer treatment technique that has shown promising potential for bladder cancer treatment. The position of the bladder cancer at different locations along the bladder wall lining can potentially affect the treatment efficacy since laser is irradiated externally from the skin surface. The present study investigates the efficacy of GNR-PTT in the treatment of bladder cancer in mice for tumours growing at three different locations on the bladder, i.e., Case 1: closest to skin surface, Case 2: at the bottom half of the bladder, and Case 3: at the side of the bladder. Investigations were carried out numerically using an experimentally validated framework for optical-thermal simulations. An in-silico approach was adopted due to the flexibility in placing the tumour at a desired location along the bladder lining. Results indicate that for the treatment parameters considered (laser power 0.3 W, GNR volume fraction 0.01% v/v), only Case 1 can be used for an effective GNR-PTT. No damage to the tumour was observed in Cases 2 and 3. Analysis of the thermo-physiological responses showed that the effectiveness of GNR-PTT in treating bladder cancer depends not only on the depth of the tumour from the skin surface, but also on the type of tissue that the laser must pass through before reaching the tumour. In addition, the results are reliant on GNRs with a diameter of 10 nm and an aspect ratio of 3.8 - tuned to exhibit peak absorption for the chosen laser wavelength. Results from the present study can be used to highlight the potential for using GNR-PTT for treatment of human bladder cancer. It appears that Cases 2 and 3 suggest that GNR-PTT, where the laser passes through the skin to reach the bladder, may be unfeasible in humans. While this study shows the feasibility of using GNRs for photothermal ablation of bladder cancer, it also identifies the current limitations needed to be overcome for an effective clinical application in the bladder cancer patients.

Cheong JK ，Popov V ，Alchera E ，Locatelli I ，Alfano M ，Menichetti L ，Armanetti P ，Maturi M ，Franchini MC ，Ooi EH ，Chiew YS ... -  《-》

Gold nanorods assisted photothermal therapy of bladder cancer in mice: A computational study on the effects of gold nanorods distribution at the centre, periphery, and surface of bladder cancer.

Gold nanorod-assisted photothermal therapy (GNR-PTT) is a cancer treatment whereby GNRs incorporated into the tumour act as photo-absorbers to elevate the thermal destruction effect. In the case of bladder, there are few possible routes to target the tumour with GNRs, namely peri/intra-tumoural injection and intravesical instillation of GNRs. These two approaches lead to different GNR distribution inside the tumour and can affect the treatment outcome. The present study investigates the effects of heterogeneous GNR distribution in a typical setup of GNR-PTT. Three cases were considered. Case 1 considered the GNRs at the tumour centre, while Case 2 represents a hypothetical scenario where GNRs are distributed at the tumour periphery; these two cases represent intratumoural accumulation with different degree of GNR spread inside the tumour. Case 3 is achieved when GNRs target the exposed tumoural surface that is invading the bladder wall, when they are delivered by intravesical instillation. Results indicate that for a laser power of 0.6 W and GNR volume fraction of 0.01%, Case 2 and 3 were successful in achieving complete tumour eradication after 330 and 470 s of laser irradiation, respectively. Case 1 failed to form complete tumour damage when the GNRs are concentrated at the tumour centre but managed to produce complete tumour damage if the spread of GNRs is wider. Results from Case 2 also demonstrated a different heating profile from Case 1, suggesting that thermal ablation during GNR-PTT is dependant on the GNRs distribution inside the tumour. Case 3 shows similar results to Case 2 whereby gradual but uniform heating is observed. Cases 2 and 3 show that uniformly heating the tumour can reduce damage to the surrounding tissues. Different GNR distribution associated with the different methods of introducing GNRs to the bladder during GNR-PTT affect the treatment outcome of bladder cancer in mice. Insufficient spreading during intratumoural injection of GNRs can render the treatment ineffective, while administered via intravesical instillation. GNR distribution achieved through intravesical instillation present some advantages over intratumoural injection and is worthy of further exploration.

Cheong JK ，Ooi EH ，Chiew YS ，Menichetti L ，Armanetti P ，Franchini MC ，Alchera E ，Locatelli I ，Canu T ，Maturi M ，Popov V ，Alfano M ... -  《-》

Thermal analysis of laser irradiation-gold nanorod combinations at 808 nm, 940 nm, 975 nm and 1064 nm wavelengths in breast cancer model.

Bianchi L ，Mooney R ，Cornejo YR ，Schena E ，Berlin JM ，Aboody KS ，Saccomandi P ... -  《-》