A 2D nanotheranostic platform based on graphene oxide and phase-change materials for bimodal CT/MR imaging, NIR-activated drug release, and synergistic thermo-chemotherapy.

Recent years have seen considerable progress in the development of nanomedicine by the advent of 2D nanomaterials serving as ideal platforms to integrate multiple theranostic functions. We synthesized multifunctional stimuli-responsive 2D-based smart nanocomposites (NCs), comprising gold nanoparticles (AuNPs) and superparamagnetic iron oxides (SPIOs) scaffolded within graphene oxide (GO) nanosheets, coated with doxorubicin (DOX)-loaded 1-tetradecanol (TD), and further modified with an alginate (Alg) polymer. TD is a phase-change material (PCM) that confines DOX molecules to the GO surface and melts when the temperature exceeds its melting point (Tm=39 °C), causing the PCM to release its drug payload. By virtue of their strong near-infrared (NIR) light absorption and high photothermal conversion efficiency, GO nanosheets may enable photothermal therapy (PTT) and activate a phase change to trigger DOX release. Upon NIR irradiation of NCs, a synergistic thermo-chemotherapeutic effect can be obtained by GO-mediated PTT, resulting an accelerated and controllable drug release through the PCM mechanism. The biodistribution of these NCs could also be imaged with computed tomography (CT) and magnetic resonance (MR) imaging in vitro and in vivo. Hence, this multifunctional nanotheranostic platform based on 2D nanomaterials appears a promising candidate for multimodal image-guided cancer therapy.

Magneto-plasmonic nanoparticle mediated thermo-radiotherapy significantly affects the nonlinear optical properties of treated cancer cells.

In order to determine the level of cell damage in cancerous cells, current cytogenetic tests have limitations such as time consumption and high cost. The aim of this study was to demonstrate the ability of nonlinear refractive (NLR) index as a predictor of breast cell damage caused by magneto-plasmonic nanoparticle based thermo-radiotherapy treatments. MCF-7 breast cancer cells were subjected individually to the treatment of radiation, radio-frequency (RF) hyperthermia, and radiation + RF hyperthermia. These treatments were repeated in the presence of magneto-plasmonic nanoparticle (Au@IONP). The MTT and nonlinear optical assays were used to evaluate the damage induced by different treatment modalities. The results of MTT were correlated with Z-scan, as the magnitude of nonlinear refraction increased with higher intensity of induced cell damages. In this regard, the lowest cell viability (38 %,) and highest magnitude of NLR index (+28.12) were obtained from combination of radiation (at 4 Gy dose) and hyperthermia treatment in the presence of nanoparticles. The proposed optical index (NLR) indicated high capability and can be used as an auxiliary tool to monitor induced cell damage during different treatment strategies. This technique is fast, noninvasive, does not impose cost, and finally does not waste materials.

MRI-based numerical modeling strategy for simulation and treatment planning of nanoparticle-assisted photothermal therapy.

Nanoparticle-assisted photothermal therapy (NPTT) has recently emerged as a promising alternative to traditional thermal therapy methods. Computational modeling for simulation and treatment planning of NPTT seems to be essential for clinical translation of this modality. Non-invasive identification of nanoparticle distribution within the tissue is a key perquisite for accurate prediction of NPTT in real conditions. In the present study, we have developed a magnetic resonance imaging (MRI)-based numerical modeling strategy for simulation and treatment planning of NPTT. To this end, we have utilized the core-shell γ-Fe2O3@Au nanoparticle comprising a gold layer with plasmonic properties and a magnetic core that enables to track the location of this structure via MRI. The map of nanoparticle distribution in the tumor derived from T2-weighted MR image was imported into a finite element simulation software, and Pennes bioheat equation and Arrhenius damage model were applied to simulate the temperature and damage distributions, respectively. The validation of the model developed herein was assessed by monitoring the superficial and the central temperature variations of the tumor in experiment. Both the numerical modeling and experimental study proved that a localized heating and then a focused damage could be achieved due to nanoparticle inclusion. There is quite satisfactory agreement between the numerical and experimental results. The model developed in this study has a good capability to be used as a promising planning method for NPTT of cancer.

Simulation-guided photothermal therapy using MRI-traceable iron oxide-gold nanoparticle.

Despite the immense benefits of nanoparticle-assisted photothermal therapy (NPTT) in cancer treatment, the limited method and device for detecting temperature during heat operation significantly hinder its overall progress. Development of a pre-treatment planning tool for prediction of temperature distribution would greatly improve the accuracy and safety of heat delivery during NPTT. Reliable simulation of NPTT highly relies on accurate geometrical model description of tumor and determining the spatial location of nanoparticles within the tissue. The aim of this study is to develop a computational modeling method for simulation of NPTT by exploiting the theranostic potential of iron oxide­gold hybrid nanoparticles (IO@Au) that enable NPTT under magnetic resonance imaging (MRI) guidance. To this end, CT26 colon tumor-bearing mice were injected with IO@Au nanohybrid and underwent MR imaging. The geometrical model description of tumor and nanoparticle distribution map were obtained from MR image of the tumor and involved in finite element simulation of heat transfer process. The experimental measurement of tumor temperature confirmed the validity of the model to predict temperature distribution. The constructed model can help to predict temperature distribution during NPTT and then allows to optimize the heating protocol by adjusting the treatment parameters prior to the actual treatment operation.

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 mm2 (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.