Investigating the mechanisms behind extensive death in human cancer cells following nanoparticle assisted photo-thermo-radiotherapy

We have recently reported the synthesis and characterization of gold-coated iron oxide nanoparticle and demonstrated such a nanoparticle (Au@Fe2O3 NP) was able to significantly enhance the lethal effects of photo-thermo-radiotherapy. The purpose of this study was to determine the mechanisms behind such an enhancement by investigating the changes induced in cancer cell viability, proliferation, and morphology as well as monitoring the alteration of some genes which play important role in the process of cell death. Using MTT assay and transmission electron microscopy (TEM), the KB cells viability and morphology were assessed after treating with various combinations of NPs, photothermal therapy (PTT), and radiotherapy (RT). Clonogenic assay was used to assess the proliferation ability of treated KB cells. Nanoparticle internalization into the cells was investigated by TEM and inductively coupled plasma (ICP). During the treatment procedures, temperature changes were monitored using an IR-camera. Furthermore, the changes occurred in Bax, BCL2 and HSP70 genes expression level were measured using real-time PCR. The results showed that combination of NP, PTT, and RT caused more cell death compared to PTT or RT alone. Following such a combination therapy, massive cell injury was detected. We also observed an extensive increase in Bax/Bcl2 ratio and HSP70 expression for the KB cells treated by combination therapy procedure. Our results showed that massive cell injury and apoptosis induction are the main reasons of extensive cell death observed in cancer cells when a nanoparticle assisted photo-thermo-radiotherapy procedure is applied. © 2019 Elsevier B.V

Multifunctional Theranostic Graphene Oxide Nanoflakes as MR Imaging Agents with Enhanced Photothermal and Radiosensitizing Properties

The integration of multiple therapeutic and diagnostic functions into a single nanoplatform for image-guided cancer therapy has been an emerging trend in nanomedicine. We show here that multifunctional theranostic nanostructures consisting of superparamagnetic iron oxide (SPIO) and gold nanoparticles (AuNPs) scaffolded within graphene oxide nanoflakes (GO-SPIO-Au NFs) can be used for dual photo/radiotherapy by virtue of the near-infrared (NIR) absorbance of GO for photothermal therapy (PTT) and the Z element radiosensitization of AuNPs for enhanced radiation therapy (RT). At the same time, this nanoplatform can also be detected by magnetic resonance (MR) imaging because of the presence of SPIO NPs. Using a mouse carcinoma model, GO-SPIO-Au NF-mediated combined PTT/RT exhibited a 1.85-fold and 1.44-fold higher therapeutic efficacy compared to either NF-mediated PTT or RT alone, respectively, resulting in a complete eradication of tumors. As a sensitive multifunctional theranostic platform, GO-SPIO-Au NFs appear to be a promising nanomaterial for enhanced cancer imaging and therapy. © 2021 American Chemical Society

Modulation of cancer cells� radiation response in the presence of folate conjugated Au@Fe 2 O 3 nanocomplex as a targeted radiosensitizer

Objectives: To investigate the effects of Au@Fe 2 O 3 core�shell nanoparticle (NP), with and without conjugation to folic acid (FA) as a targeting ligand, on radiosensitization of both cancer and healthy cells. Methods: Au@Fe 2 O 3 NPs were first synthesized, then modified with FA, and finally characterized. Radiation dose enhancement studies were performed on KB cancer cells and L929 healthy cells. NPs at the concentration of 20 µg/ml were first incubated with both cell lines and then different doses of 6 MV X-ray radiation were examined. The end effects were evaluated via MTT assay and flow cytometry using AnnexinV/PI kit. Results: It was indicated that viability of KB cells has a much lower rate than L929 cells when the cells were treated by (FA-Au@Fe 2 O 3 ) + (X-ray) regimen. Cell viability was even decreased significantly when X-ray dose increased. Moreover, flow cytometry studies revealed that FA-targeted NPs induced higher level of apoptosis for KB cancer cells than L929 healthy cells. Conclusion: Our findings provide a new perspective on high ability of the synthesized FA-targeted Au@Fe 2 O 3 NPs which may be considered as an efficient radiosensitizer in the process of targeted radiation therapy of cancer. © 2018, Federación de Sociedades Españolas de Oncología (FESEO)

Optimal scheduling of the nanoparticle-mediated cancer photo-thermo-radiotherapy

Maximal synergistic effect between photothermal therapy and radiotherapy (RT) may be achieved when the interval between these two modalities is optimal. In this study, we tried to determine the optimal schedule of the combined regime of RT and nano-photothermal therapy (NPTT), based on the cell cycle distribution and kinetics of cell death. To this end, alginate-coated iron oxide-gold core-shell nanoparticles (Fe3O4@Au/Alg NPs) were synthesized, characterized, and their photo-radio sensitization potency was evaluated on human nasopharyngeal cancer KB cells. Our results demonstrated that synthesized NPs have a good potential in radiotherapy and near-infrared (NIR) photothermal therapy. However, results from flow cytometry analysis indicated that a major portion of KB cells were accumulated in the most radiosensitive phases of cell cycle (G2/M) 24 h after NPTT. Moreover, the maximal synergistic anticancer efficacy (12.3 cell viability) was observed when RT was applied 24 h following the administration of NPTT (NPs 30 μg/mL, 4 h incubation time + Laser 808 nm, 1 W/cm2, 5 min + RT 6 Gy). It is noteworthy that apoptosis was the dominant cell death pathway in the group of cells treated by combination of NPTT and RT. This highly synergistic anticancer efficacy provides a mechanistic basis for Fe3O4@Au/Alg NPs-mediated photothermal therapy combined with RT. Knowing such a basis is helpful to promote novel nanotechnology cancer treatment strategies. © 2020 Elsevier B.V

Ultrastructural and optical characteristics of cancer cells treated by a nanotechnology based chemo-photothermal therapy method

The current chemotherapy method demonstrates the need for improvement in terms of efficacy and safety. Given the beneficiary effect of heat in combination with chemotherapy, the purpose of this study is to develop a multifunctional nanoplatform by co-incorporating gold nanoparticles (AuNPs) as photothermal agent and cisplatin as anticancer drug into alginate hydrogel (named as ACA) to enable concurrent thermo-chemotherapy. The in vitro cytotoxicity experiment showed that the as-developed nanocomplex was able to induce greater cytotoxicity in KB human nasopharyngeal cancer cells compared to free cisplatin at the same concentration. Moreover, the interaction of ACA and laser irradiation acted synergistically and resulted in higher cell death rate compared to separate application of photothermal therapy and chemotherapy. The micrograph of KB cells also revealed that ACA was able to selectively accumulate into the mitochondria, so that laser irradiation of KB cells pre-treated with ACA resulted in intensive morphological damages such as plasma membrane disruption, chromatin condensation, autophagic vacuoles formation and organelle degeneration. Moreover, the sign and magnitude of optical nonlinear refractive index measured by Z-scan technique was shown to be significantly altered in cells exposed to ACA with and without laser irradiation. Consequently, the nanocomplex developed herein could be a promising platform to combine photothermal therapy and chemotherapy effectively, thereby achieving synergistic therapeutic outcome. © 2019 Elsevier B.V

Genetically diabetic animals.

Several animal species, mostly rodents, were described to exhibit spontaneously diabetes mellitus on a hereditary basis. These findings were highly appreciated with the expectation to get more insight into the pathogenesis of diabetes in humans. During the last few years since the discovery of leptin (Zhang et al. 1994) and its downstream signal transduction cascade (Friedman and Halaas 1998), tremendous new insight of the genetics of diabetic and obese animal disease models was derived. Up to now, at least six genetically diabetic animal models exhibit defects in the leptin pathway: the ob mutation in the mouse resulted in leptin deficiency. The db mutation in the mouse and the cp and fa mutations in the rat are different mutations of the leptin receptor gene. The fat mutation in the mouse results in a biologically inactive carboxypeptidase E, which processes the prohormone conversion of POMC into α-MSH, which activates the hypothalamic MC4 receptor. Finally the Agouti yellow (y) mouse exhibit a ubiquitous expression of the Agouti protein which represents an antagonist of the hypothalamic MC4 receptor