Real-time mapping of heat generation and distribution in a laser irradiated agar phantom loaded with gold nanoparticles using MR temperature imaging

Gold nanoparticles (AuNPs) have shown potential strength in photothermal therapy of cancer. Several techniques have been developed to investigate local heat generation by AuNPs. However, a sensitive thermal imaging technology with high temporal resolution, minimum invasiveness and high spatial resolution is still lacking. In this research study, by using magnetic resonance thermal imaging (MRTI), we reported a technique for monitoring of heat generation and distribution in an AuNPs loaded agar phantom irradiated by laser. Three different agar phantoms with various AuNPs concentrations (0, 8 and 16 μg/ml) were produced and studied. The phantoms were exposed to an external laser 532 nm; 4 min under MRTI. For real-time temperature monitoring, we employed the theory of proton resonance frequency (PRF) shift. Infrared (IR) camera was employed to measure the actual temperature of each point on the surface of irradiated agar gel. Finally, the correlation between the temperatures obtained by IR camera and MRTI was evaluated. We observed that temperature of the gels loaded by AuNPs at concentration of 0, 8 and 16 μg/ml reached 27.2, 37.8, 45 °C with a total area of heat distribution of 94.98, 452.16, and 907.34 mm 2 (from the point of irradiation). During the process of laser irradiation, we observed: (i) a significant rise in temperature, (ii) a dependency between the rate of temperature rise and concentration of AuNPs, and (iii) a direct correlation between temperature change and MR image phase. In addition, statistical analysis showed that the variation of temperatures measured by IR camera and temperatures computed by MRTI had acceptable correlation (R > 0.9). In conclusion, MRTI has a good sensitivity and precision that can be employed for nano-photothermal therapy planning and may be considered for real-time mapping of heat generation and distribution in a laser irradiated tissue loaded by AuNPs. © 2018 Elsevier B.V

A thermo-responsive alginate nanogel platform co-loaded with gold nanoparticles and cisplatin for combined cancer chemo-photothermal therapy

The current interest in cancer research is being shifted from individual therapy to combinatorial therapy. In this contribution, a novel multifunctional nanoplatform comprising alginate nanogel co-loaded with cisplatin and gold nanoparticles (AuNPs) has been firstly developed to combine photothermal therapy and chemotherapy. The antitumor efficacy of the as-prepared nanocomplex was tested against CT26 colorectal tumor model. The nanocomplex showed an improved chemotherapy efficacy than free cisplatin and caused a significantly higher tumor inhibition rate. The in vivo thermometry results indicated that the tumors treated with the nanocomplex had faster temperature rise rate under 532 nm laser irradiation and received dramatically higher thermal doses due to optical absorption properties of AuNPs. The combined action of chemo-photothermal therapy using the nanocomplex dramatically suppressed tumor growth up to 95 of control and markedly prolonged the animal survival rate. Moreover, tumor metabolism was quantified by 18 FFDG (2-deoxy-2- 18 Ffluoro-D-glucose)-positron emission tomography (PET) imaging and revealed that the combination of the nanocomplex and laser irradiation have the potential to eradicate microscopic residual tumor to prevent cancer relapse. Therefore, the nanocomplex can afford a potent anticancer efficacy whereby heat and drug can be effectively deliver to the tumor, and at the same time the high dose-associated side effects due to the separate application of chemotherapy and thermal therapy could be potentially reduced. © 2019 Elsevier Lt

Gold nanoparticles promote a multimodal synergistic cancer therapy strategy by co-delivery of thermo-chemo-radio therapy

Multimodal cancer therapy has become a new trend in clinical oncology due to potential generation of synergistic therapeutic effects. Herein, we propose a multifunctional nanoplatform comprising alginate hydrogel co-loaded with cisplatin and gold nanoparticles (abbreviated as ACA) for triple combination of photothermal therapy, chemotherapy and radiotherapy (thermo-chemo-radio therapy). The therapeutic potential of ACA was assessed in combination with 532 nm laser and 6 MV X-ray against KB human mouth epidermal carcinoma cells. The results demonstrated that tri-modal thermo-chemo-radio therapy using ACA induced a superior anticancer efficacy than mono- or bi-modality treatments. The intracellular reactive oxygen species (ROS) level in KB cells treated with tri-modal therapy was increased by 4.4-fold compared to untreated cells. The gene expression analysis demonstrated the up-regulation of Box pro-apoptotic factor (by 4.5-fold) and the down-regulation of Bcl-2 anti-apoptotic factor (by 0.3-fold). The massive cell injury and the appearance of morphological characteristics of apoptosis were also evident in the micrograph of KB cells caused by thermo-chemo-radio therapy. Therefore, ACA nanocomplex can be offered as a promising platform to combine photothermal therapy, chemotherapy and radiotherapy, thereby affording an opportunity for combating chemo- and radio-resistant tumors