A machine learning approach for prediction of auditory brain stem response in patients after head-and-neck radiation therapy.

Objective: The present study aimed to assess machine learning (ML) models according to radiomic features to predict ototoxicity using auditory brain stem responses (ABRs) in patients with radiation therapy (RT) for head-and-neck cancers. Materials and Methods: The ABR test was performed on 50 patients having head-and-neck RT. Radiomic features were extracted from the brain stem in computed tomography images to generate a radiomic signature. Moreover, accuracy, sensitivity, specificity, the area under the curve, and mean cross-validation were used to evaluate six different ML models. Results: Out of 50 patients, 21 participants experienced ototoxicity. Furthermore, 140 radiomic features were extracted from the segmented area. Among the six ML models, the Random Forest method with 77% accuracy provided the best result. Conclusion: According to the ML approach, we showed the relatively high prediction power of the radiomic features in radiation-induced ototoxicity. To better predict the outcomes, future studies on a larger number of participants are recommended.

Radiosensitising effect of iron oxide-gold nanocomplex for electron beam therapy of melanoma in vivo by magnetic targeting.

Melanoma is a dangerous type of skin cancer sometimes treated with radiotherapy. However, it induces damage to the surrounding healthy tissue and possibly further away areas. Therefore, it is necessary to give a lower dose to the patient with targeted therapy. In this study, the radio-sensitising effect of gold-coated iron oxide nanoparticles on electron beam radiotherapy of a melanoma tumour with magnetic targeting in a mouse model was investigated. Gold-coated iron oxide nanoparticles were prepared in a steady procedure. The melanoma tumour model was induced in mice. Animals were divided into five groups: (1) normal; (2) melanoma; (3) gold-coated iron oxide nanoparticles alone; (4) electron beam radiotherapy; (5) electron beam radiotherapy plus gold-coated iron oxide nanoparticles. The magnet was placed on the tumour site for 2 h. The tumours were then exposed to 6 MeV electron beam radiotherapy for a dose of 8 Gy. Inductively coupled plasma optical emission spectrometry test, hematoxylin and eosin staining, and enzyme-linked immunosorbent assay blood test were also performed. Gold-coated iron oxide nanoparticles with magnetic targeting before electron beam radiotherapy reduced the growth of the tumour compared to the control group. Blood tests did not show any significant toxicity. Deposition of nanoparticles was more in the tumour and spleen tissue and to a lesser extent in the liver, kidney, and lung tissues. The synergistic effect of nanoparticles administered by the intraperitoneal route and then concentrated into the tumour area by application of an external permanent magnet, before delivery of the electron beam radiotherapy improved the overall cancer treatment outcome and prevented metal distribution side effects.

Chemo-radiation therapy of U87-MG glioblastoma cells using SPIO@AuNP-Cisplatin-Alginate nanocomplex.

Megavoltage radiotherapy and cisplatin-based chemotherapy are the primary glioblastoma treatments. Novel nanoparticles have been designed to reduce adverse effects and boost therapeutic effectiveness. In the present study, we synthesized the SPIO@AuNP-Cisplatin-Alginate (SACA) nanocomplex, composed of a SPIO core, a gold shell, and an alginate coating. SACA was characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS). U87-MG human glioblastoma cells and the HGF cell line (a healthy primary gingival fibroblast) were treated in multiple groups by a combination of SACA, cisplatin, and 6 MV X-ray. The MTT assay was used to assess the cytotoxicity of cisplatin and SACA (at various concentrations and for 4 h). Following the treatments, apoptosis and cell viability were evaluated in each treatment group using flow cytometry and the MTT assay, respectively. The findings demonstrated that the combination of SACA and 6 MV X-rays (at the doses of 2 and 4 Gy) drastically decreased the viability of U87MG cells, whereas the viability of HGF cells remained unchanged. Moreover, U87MG cells treated with SACA in combination with radiation exhibited a significant increase in apoptosis, demonstrating that this nanocomplex effectively boosted the radiosensitivity of cancer cells. Even though additional in vivo studies are needed, these findings suggest that SACA might be used as a radiosensitizer nanoparticle in the therapy of brain tumors.

Folate functionalized gold-coated magnetic nanoparticles effect in combined electroporation and radiation treatment of HPV-positive oropharyngeal cancer.

The rate of HPV-positive oropharyngeal cancer incidence is increasing, especially in the young population. While these patients show good responses to radiotherapy. The major complication of radiotherapy is normal tissue involvement. Thus, finding an effective treatment method is essential. Multimodal therapy with the lowest side effect could be an effective treatment method. Theranostic gold magnetic core-shell nanostructure was developed as a platform for multimodal therapy of HPV-positive oropharyngeal cancer. The folate functionalized gold-magnetic core-shell nanostructure has been synthesized in a stepwise approach and characterized with various techniques including TEM, UV-Vis, and FTIR spectroscopy. KB was selected as a host for HPV and folate receptor-positive cancer. HGF as normal cell lines was selected. Both cell lines have been treated with nanoparticles, electric field and radiotherapy, either separately or in combination. Cell viability and apoptosis rate were determined by MTT and flow cytometry assay. In addition, cellular uptake of the nanoparticles was measured by ICP-OES analysis. The average size of folate functionalized gold-magnetic core-shell nanostructure was 13.8 ± 6.4 nm. A characteristic plasmonic peak of gold nanoshells was observed in the UV-Vis spectrum. The functionalization of synthesized nanostructure was confirmed with FTIR spectroscopy. None of the treatments alone can cause a significant death in cancerous cells. Combination treatments can increase cancer cell mortality and increase the proportion of apoptotic cells in them. Furthermore, it has been observed that the electric field enhanced the cellular uptake of nanoparticles just in cancerous cells. Based on our findings, we conclude that the combination of folate functionalized nanoparticles and electroporation opens a new way to improve radiation therapy efficacy of HPV-positive cancers.

Dual electrochemical sensing of spiked virus and SARS-CoV-2 using natural bed-receptor (MV-gal1).

It has been necessary to use methods that can detect the specificity of a virus during virus screening. In this study, we use a dual platform to identify any spiked virus and specific SARS-CoV-2 antigen, sequentially. We introduce a natural bed-receptor surface as Microparticle Vesicle-Galactins1 (MV-gal1) with the ability of glycan binding to screen every spiked virus. MV are the native vesicles which may have the gal-1 receptor. Gal-1 is the one of lectin receptor which can bind to glycan. After dropping the MV-gal1 on the SCPE/GNP, the sensor is turned on due to the increased electrochemical exchange with [Fe(CN)6]-3/-4 probe. Dropping the viral particles of SARS-CoV-2 cause to turn off the sensor with covering the sugar bond (early screening). Then, with the addition of Au/Antibody-SARS-CoV-2 on the MV-gal1@SARS-CoV-2 Antigen, the sensor is turned on again due to the electrochemical amplifier of AuNP (specific detection).For the first time, our sensor has the capacity of screening of any spike virus, and the specific detection of COVID-19 (LOD: 4.57 × 102 copies/mL) by using the natural bed-receptor and a specific antibody in the point of care test.

Investigating the in vitro photothermal effect of green synthesized apigenin-coated gold nanoparticle on colorectal carcinoma.

Applying toxic chemical to the synthesis of stable gold nanoparticles is one of the limitations of gold nanoparticles for therapeutic applications such as photothermal therapy. Plant compounds such as apigenin (API) with therapeutic potential can be applied in the synthesis of gold nanoparticles. API-coated gold nanoparticles (Api@AuNPs) with an average size of 19.1 nm and a surface charge of -4.3 mV have been synthesized by a simple and efficient technique. The stability of Api@AuNPs in the biological environment was verified through UV-Vis spectroscopy. Based on Raman and FTIR spectroscopy analysis, chemical binding of API on the surface of Api@AuNPs through hydroxyl and carbonyl functional groups was found to be the main reason for the stability of the Api@AuNPs in comparison with citrate-coated gold nanoparticles (Cit@AuNPs). The synthesized Api@AuNPs do not cause major toxic effects up to 128 ppm. Api@AuNP-mediated photothermal therapy leads to the indiscriminate eradication of almost half of both mouse fibroblastic (L929) and colorectal cancer (CT26) cells. Flow-cytometry analysis revealed that the cell death mechanism is mainly apoptosis. In the apoptosis triggered cell death in photothermal treatment, Api@AuNPs are preferred over commonly used gold nanoparticles in photothermal treatments which mostly trigger the necrosis cell death pathway.

Photobiomodulation for spinal cord injury: A systematic review and meta-analysis.

In recent years, photobiomodulation therapy (PBMT) has found many applications in various medical fields. Studies of PBMT on spinal cord injury (SCI) have mostly used laser sources in experimental animal models. The purpose of this study was to summarize studies that have employed PBMT for various kinds of SCI in animals. A thorough search in databases including MEDLINE, EMBASE, SCOPUS, and Web of Science, with the removal of unrelated articles, yielded 16 relevant articles. The meta-analysis showed that PBMT was effective in improving post-SCI movement in the first 14 days (MD = 1.593 (95% CI: 1.110 to 2.075; p <0.001, I2 = 51.9%) and this improvement became even greater thereafter (MD = 2.086 (95% CI: 1.570 to 2.603; p = <0.001. I2= 90.3%). Time of irradiation (<300 sec or >300 sec), gender (male or female), injury model (contusion or compression, radiation protocol (<14 days or ≥14days), laser wavelength (<800nm or >800nm) and injury severity (moderate or severe) were found to be factors that can affect PBM efficacy for SCI treatment. PBMT has an anti-inflammatory effect, is effective in reducing the size of spinal cord lesions and helps to absorb administrated proteins and stem cells to the lesion site.

Different liposome patterns to detection of acute leukemia based on electrochemical cell sensor.

Leukemia is the worst type of malignancy in children which its proper diagnosis can be used in the treatment. We design the turn-off sensor by using the different electrochemical patterns of liposomes to the detection of acute lymphoblastic leukemia cells. Our design is first sandwiched by lectin liposome which increases the electrochemical exchange on the electrode. With the addition of Molt-4 cells, the bonding connection between the n-glycan and lectin can also increase the electrochemical exchange with the high detection cells. Subsequently, the addition of boronic acid liposomes decreases the resistance due to covering glycosylation bond and the sensor is turn-off. But stable and specific binding with the sialic acid causes the higher detection of Molt-4 cells. The electrochemical measurements are performed between the potentials at -0.4 V and +0.4 V with 1 mM [Fe(CN)6] -3/-4. So, for the first time, we designed a cells sensor based on the different patterns of liposomes to screening the N-glycan cells, which can be used in the point of care tests with higher sensitivity.

Design of a DOPC-MoS2/AuNP hybrid as an organic bed with higher amplification for miR detection in electrochemical biosensors.

The liposome-based biosensors are used for detection of nucleic acids and proteins as organic beds which are biocompatible tools for point of care tests, but their lack of sensitivity has been challenging. Therefore, designing a proper strategy is vital to increase the sensitivity of the target in diagnostic tests. In this study, for the first time, we use a combination of cationic DOPC liposome (dioleoylphosphatidylcholine) with MoS2 to enhance the sensitivity of liposomal sensors clearly. The electrochemical measurements are performed between potentials at - 0.4 V and + 0.4 V with 1 mM [Fe(CN)6]-3/-4. At first, we construct the DOPC/MoS2 hybrid (as a mineral/organic bed) to promote higher electrochemical behavior than DOPC liposome (as organic bed). In this research, adding AuNP can cause attachment with both the DOPC and MoS2. Therefore, the electrochemical reactions are enhanced accordingly to provide more positions for attaching the probes on the AuNP. So our DOPC-MoS2/AuNP hybrid can detect miR-21 with high sensitivity (LOD = 10 aM) because of attachment of miR-21 to MoS2/AuNP in addition to DOPC/AuNP. This sensor has also high specificity and repeatability as a biocompatible sensor, which can be used in point of care tests and transduction instruments.

Organ at risk dose calculation for left sided breast cancer treatments using intraoperative electron radiotherapy: A Monte Carlo-based feasibility study.

The present study aims to calculate the received dose by lungs and heart, as organs at risk (OAR), during intraoperative electron radiotherapy (IOERT) of left breast cancer at the presence and absence of shielding disk using Monte Carlo (MC) simulation. LIAC 12, a dedicated IOERT Linac, and an anthropomorphic phantom were considered in this study to simulate particle tracks of 6, 8, 10, and 12 MeV nominal electron energies using EGSnrc MC particle transport simulation code. The results showed that for increasing electron beam energies in the absence of shielding disk, left lung and heart dose would also be increasing so that, maximum left lung and heart dose respectively increases from 0.512 to 9.920 Gy and from 0 to 0.506 Gy with increment of electron energy from 6 to 12 MeV. Employing the shielding disk in 6 and 8 MeV energy can reduce the heart and left lung maximum dose to zero. On the other hand, this dose reduction at 10 and 12 MeV energy was respectively about 99% and 93.5% for heart and 99.9% and 92.9% for left lung. Right lung did not receive a remarkable dose both in presence and absence of shielding disk. From the results, it can be concluded that employing the shielding disk can effectively reduce the received dose to OARs.

Combinatorial effects of radiofrequency hyperthermia and radiotherapy in the presence of magneto-plasmonic nanoparticles on MCF-7 breast cancer cells.

Here, the effects of combinatorial cancer therapy including radiotherapy (RT) and radiofrequency (RF) hyperthermia in the presence of gold-coated iron oxide nanoparticles (Au@IONPs), as a thermo-radio-sensitizer, are reported. The level of cell death and the ratio of Bax/Bcl2 genes, involved in the pathway of apoptosis, were measured to evaluate the synergistic effect of Au@IONPs-mediated RF hyperthermia and RT. MCF-7 human breast adenocarcinoma cells were treated with different concentrations of Au@IONPs. After incubation with NPs, the cells were exposed to RF waves (13.56 MHz; 100 W; 15 min). At the same time, thermometry was performed with an infrared (IR) camera. Then, the cells were exposed to 6 MV X-ray at various doses of 2 and 4 Gy. MTT (3-[4,5-dimethylthiazol-2-y1]-2,5-diphenyltetrazolium bromide) assay was performed to evaluate cell viability and quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expression ratio of Bax/Bcl2. Cellular uptake of nanoparticles was confirmed qualitatively and quantitatively. The results obtained from MTT assay and qRT-PCR studies showed that NPs and RF hyperthermia had no significant effect when applied separately, while their combination had synergistic effects on cell viability percentage and the level of apoptosis induction. A synergistic effect was also observed when the cancer cells were treated with a combination of NPs, RF hyperthermia, and RT. On the basis of the obtained results, it may be concluded that the use of magneto-plasmonic NPs in the process of hyperthermia and RT of cancer holds a great promise to develop a new combinatorial cancer therapy strategy.

Gold-coated iron oxide nanoparticles trigger apoptosis in the process of thermo-radiotherapy of U87-MG human glioma cells.

Recently, gold-coated iron oxide nanoparticles (Au@IONPs) have received a great deal of attention in cancer therapy. In this in vitro study we aimed to investigate the anti-cancer effects of Au@IONPs core-shell nanoparticles when applied in thermo-radiotherapy. Moreover, we investigated the level of apoptosis induced in U87-MG human glioma cells after receiving a combinatorial treatment regimen (Au@IONPs + hyperthermia + radiotherapy). Firstly, the Au@IONPs nanocomplex was prepared and characterized. Cytotoxicity of the nanoparticles (various concentrations; 4 h incubation time) was investigated on U87-MG cells and finally the concentrations of 10 and 15 µg/mL were selected for further studies. After incubation of the cells with nanoparticles, they received hyperthermia (43 °C; 1 h) and then were immediately exposed to 6 MV X-ray (2 and 4 Gy). Following the treatments, MTT assay was used to analyze cell viability and flow cytometry was used to determine the level of apoptosis in each treatment group. The results revealed that nanoparticles have no significant cytotoxicity at concentrations lower than 10 µg/mL. Also, we observed that nanoparticles are able to enhance the cytotoxic effect of hyperthermia and radiation. The major mode of cell death was apoptosis when nanoparticles, hyperthermia and radiation were concomitantly applied to cancer cells. In conclusion, Au@IONP nanoparticle can be considered as a good thermo-radio-sensitizer which triggers significant levels of apoptosis in cancer therapy. In this in vitro study, we report the anti-cancer effects of gold-coated iron oxide nanoparticles (Au@IONPs) when applied in thermo-radiotherapy.

Investigating the Therapeutic Effects of Alginate Nanogel Co-loaded with Gold Nanoparticles and Cisplatin on U87-MG Human Glioblastoma Cells.

BACKGROUND AND PURPOSE: It has been well-known both gold nanoparticles (AuNPs) and cisplatin are potential radiosensitizers for radiotherapy of cancer. In this in vitro study, we investigated the chemoradiotherapeutic effects of alginate nanogel co-loaded with AuNPs and cisplatin (ACA) on U87-MG human glioblastoma cells. METHODS: Based on the accomplished pilot studies, U87-MG cells were incubated with ACA and cisplatin at 10% inhibitory concentration (IC10) for 4h. Then, the cells were irradiated to different doses of 6MV X-rays (2 and 10 Gy). MTT assay was performed to evaluate the cell survival rate. Apoptosis was determined by flow cytometry using an annexinV-fluorescein isothiocyanate/propidium iodide apoptosis detection kit. RESULTS: The results showed that ACA at the concentration of 4 µg/ml (per cisplatin) and free cisplatin at concentration of 15 µg/ml have the same effects on U87-MG cells (survival rate: 90%). The combination of ACA with radiation resulted in a significant decrease in cell viability (survival rate: 30%). The flow cytometry assay also showed that such a combination therapy induces more apoptosis than necrosis. CONCLUSION: It may be concluded that co-delivery of AuNPs and cisplatin with a single nanoplatform like ACA nanocomplex enhances the therapeutic ratio of human glioblastoma radiation therapy.

Photothermal therapy using folate conjugated gold nanoparticles enhances the effects of 6MV X-ray on mouth epidermal carcinoma cells.

The aim of this study was to develop an optimized method for preparation of folate conjugated gold nanoparticles (F-AuNPs) and to investigate its cytotoxic effects and cell apoptosis in combination with photothermal therapy (PTT) and radiotherapy (RT) for the treatment of mouth epidermal carcinoma cells KB. For this purpose, cells were treated with synthesized F-AuNPs at different concentrations for 6h and then irradiated them with laser beam (532nm, 0.5W/cm2, 15min). After photothermal therapy, the cells were exposed to 6MV X-ray with a single dose of 2Gy. MTT assay were performed to evaluate the cell survival rate and apoptosis was determined by flow cytometry using an annexin V-fluorescein isothiocyanate/propidium iodide apoptosis detection kit. No significant cell damage or cell apoptosis from the individual treatment of laser light or F-AuNPs was observed, while viability of cells incubated with F-AuNPs and then exposed to the laser was significantly decreased. Additionally, our results demonstrated that F-AuNPs is good radiosensitizers even at a low concentration such as 20µM when megavoltage X-ray is used. Also, when KB cells were treated with F-AuNPs under both laser and X-ray irradiation, the cell viability substantially decreased more than F-AuNPs-enhanced PTT alone or F-AuNPs-enhanced RT alone. Flow cytometry assay clearly indicated that F-AuNPs-mediated photo-thermo-radio therapy significantly induced apoptosis. These results confirm that F-AuNPs is a promising and research-worthy nanoconjugate in the field of targeted photo-thermo-radiotherapy of cancer.

Radiation-induced bystander effect in non-irradiated glioblastoma spheroid cells.

Radiation-induced bystander effects (RIBEs) are detected in cells that are not irradiated but receive signals from treated cells. The present study explored these bystander effects in a U87MG multicellular tumour spheroid model. A medium transfer technique was employed to induce the bystander effect, and colony formation assay was used to evaluate the effect. Relative changes in expression of BAX, BCL2, JNK and ERK genes were analysed using RT-PCR to investigate the RIBE mechanism. A significant decrease in plating efficiency was observed for both bystander and irradiated cells. The survival fraction was calculated for bystander cells to be 69.48% and for irradiated cells to be 34.68%. There was no change in pro-apoptotic BAX relative expression, but anti-apoptotic BCL2 showed downregulation in both irradiated and bystander cells. Pro-apoptotic JNK in bystander samples and ERK in irradiated samples were upregulated. The clonogenic survival data suggests that there was a classic RIBE in U87MG spheroids exposed to 4 Gy of X-rays, using a medium transfer technique. Changes in the expression of pro- and anti-apoptotic genes indicate involvement of both intrinsic apoptotic and MAPK pathways in inducing these effects.