Grading of Gliomas by Contrast-Enhanced CT Radiomics Features.

Background: Gliomas, as Central Nervous System (CNS) tumors, are greatly common with 80% of malignancy. Treatment methods for gliomas, such as surgery, radiation therapy, and chemotherapy depend on the grade, size, location, and the patient's age. Objective: This study aimed to quantify glioma based on the radiomics analysis and classify its grade into High-grade Glioma (HGG) or Low-grade Glioma (LGG) by various machine-learning methods using contrast-enhanced brain Computerized Tomography (CT) scans. Material and Methods: This retrospective study involved acquiring and segmenting data, selecting and extracting features, classifying, analyzing, and evaluating classifiers. The study included a total of 62 patients (31 with LGG and 31 with HGG). The tumors were segmented by an experienced CT-scan technologist with 3D slicer software. A total of 14 shape features, 18 histogram-based features, and 75 texture-based features were computed. The Area Under the Curve (AUC) and Receiver Operating Characteristic Curve (ROC) were used to evaluate and compare classification models. Results: A total of 13 out of 107 features were selected to differentiate between LGGs and HGGs and to perform various classifier algorithms with different cross-validations. The best classifier algorithm was linear-discriminant with 93.5% accuracy, 96.77% sensitivity, 90.3% specificity, and 0.98% AUC in the differentiation of LGGs and HGGs. Conclusion: The proposed method can identify LGG and HGG with 93.5% accuracy, 96.77% sensitivity, 90.3% specificity, and 0.98% AUC, leading to the best treatment for glioma patients by using CT scans based on radiomics analysis.

Molecular MR Imaging of Prostate Cancer by Specified Iron Oxide Nanoparticles With PSMA-11 Peptides: A Preclinical Study.

BACKGROUND: Prostate-specific membrane antigen (PSMA) can provide a prostate cancer (PCa) detection approach in positron emission tomography (PET) using Food and Drug Administration (FDA)-approved PSMA-11 peptide. There are some studies evaluated magnetic-nanoprobes for PSMA detection by MRI, using non-FDA-approved ligands including antibodies or peptides, which are not as specific as PSMA-11. PURPOSE: To assess targeted iron oxide nanoparticles (IONPs) by PSMA-11 peptides as a potential specific nano-molecular probes to investigate a PSMA+ PCa-xenograft model by MRI. STUDY TYPE: Prospective. ANIMAL MODEL: Twenty male C57BL6 nude mice induced subcutaneously PSMA+ LNCaP cell line tumor. FIELD STRENGTH/SEQUENCE: 1.5 T, T2 -W Fast Spin echo and T2 *-W Gradient echo. ASSESSMENT: Coated IONPs with Carboxymethylated-dextran (DNPs) and with bovine serum albumin (BNPs), as well as, targeted DNPs with PSMA-11-HYNIC peptide (TDNPs) and targeted BNPs with PSMA-11-HBED peptide (TBNPs) were injected intravenously with dose 2.8 mg Fe/kg. Coronal T2 -W and the T2 *-W images were obtained before and 4 hours and 6 hours post-injection. Signal intensity (SI) and relative signal enhancement (RSE) were computed in two- and three-dimensional analyses. Histological analysis of tumors was evaluated, and the Fe distribution within the body based on atomic absorption spectroscopy was calculated. STATISTICAL TESTS: One-way ANOVA followed by Tukey's multiple comparison test, Paired-samples T-test, P < 0.05 was considered significant. RESULTS: A reduction in T2 -W SI was achieved as 22 ± 7%, 59 ± 3%, 65 ± 5%, and 78 ± 3% respectively for BNPs, TBNPs, DNPs, and TDNPs 6 hours post-injection. The most difference between targeted and non-targeted groups was observed at 6 hours for PSMA-11-HBED, and at 4 hours for PSMA-11-HYNIC. RSE indicated 88.6 ± 3.1% and 80.7 ± 3.2% enhanced contrast between tumor and muscle region for TBNPs and TDNPs on T2 *-W images. CONCLUSIONS: Both TBNPs and TDNPs are promising novel nano-molecular probes for PSMA+ PCa tumor detection. The injection dose of non-targeted IONPs can be reduced by using targeted nanoprobes three times for BNPs and two times for DNPs. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Optimizing the Radiation Treatment Planning of Brain Tumors by Integration of Functional MRI and White Matter Tractography.

Background: Diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) present the ability to selectively protect functional regions and fiber tracts of the brain when brain tumors are treated with radiotherapy. Objective: This study aimed to assess whether the incorporation of fMRI and DTI data into the radiation treatment planning process of brain tumors could prevent the neurological parts of the brain from high doses of radiation. Material and Methods: In this investigational theoretical study, the fMRI and DTI data were obtained from eight glioma patients. This patient-specific fMRI and DTI data were attained based on tumor location, the patient's general conditions, and the importance of the functional and fiber tract areas. The functional regions, fiber tracts, anatomical organs at risk, and the tumor were contoured for radiation treatment planning. Finally, the radiation treatment planning with and without fMRI & DTI information was obtained and compared. Results: The mean dose to the functional areas and the maximum doses were reduced by 25.36% and 18.57% on fMRI & DTI plans compared with the anatomical plans. In addition, 15.59% and 20.84% reductions were achieved in the mean and maximum doses of the fiber tracts, respectively. Conclusion: This study demonstrated the feasibility of using fMRI and DTI data in radiation treatment planning to maximize radiation protection of the functional cortex and fiber tracts. The mean and maximum doses significantly decreased to neurologically relevant brain regions, resulting in reducing the neuro-cognitive complications and improving the patient's quality of life.

Optimization of cobalt ferrite magnetic nanoparticle as a theranostic agent: MRI and hyperthermia.

OBJECTIVE: Magnetic nanoparticles (MNPs) are considered a theranostic agent in MR imaging, playing an effective role in inducing magnetic hyperthermia. Since, high-performance magnetic theranostic agents are characterized by superparamagnetic behavior and high anisotropy, in this study, cobalt ferrite MNPs were optimized and investigated as a theranostic agent. METHODS: CoFe2O4@Au@dextran particles were synthesized and characterized by DLS, HRTEM, SEM, XRD, FTIR, and VSM methods. After cytotoxicity evaluation, MR imaging parameters (r1, r2 and r2 / r1) were calculated for these nanostructures. Afterward, magnetic hyperthermia at the frequency of 425 kHz was applied to calculate specific loss power (SLP). RESULTS: Formation of CoFe2O4@Au@dextran was confirmed by UV-Visible spectrophotometry. On the basis of the relaxometric and hyperthermia induction findings of nanostructures in all stages of synthesis, the CoFe2O4@Au@dextran could produce the highest parameters of r2 and r2/r1 and SLP with values ​​of 389.7, 51.2 mM-1 s-1, and 2449 W/g, respectively. CONCLUSION: The formation of multi-core MNPs by dextran coating is expected to improve the magnetic properties of the nanostructure, leading to optimization of theranostic parameters, so that CoFe2O4@Au@dextran NPs can create contrast-enhanced images more than three times the clinical use and require less contrast agent, reducing side effects. Accordingly, CoFe2O4@Au@dextran can be introduced as a suitable theranostic nanostructure with optimal efficiency.

Histopathological graded liver lesions: what role does the IVIM analysis method have?

PURPOSE: This study aims to investigate three different image processing methods on quantitative parameters of IVIM sequence, as well as apparent diffusion coefficients and simple perfusion fractions, for benign and malignant liver tumors. MATERIALS AND METHODS: IVIM images with 8 b-values (0-1000 s/mm2) and 1.5 T MRI scanner in 16 patients and 3 healthy people were obtained. Next, the regions of interest were selected for malignant, benign, and healthy liver regions (50, 56, and 12, respectively). Then, the bi-exponential equation of the IVIM technique was fitted with two segmented fitting methods as well as one full fitting method (three methods in total). Using the segmented fitting method, diffusion coefficient (D) is fixed with a mono-exponential equation with b-values that are greater than 200 s/mm2. The perfusion fraction (f) can then be calculated by extrapolating, as the first method, or fitting simultaneously with the pseudo-diffusion coefficient (D*) as the second method. In the full fitting method, as the third method, all IVIM parameters were obtained simultaneously. The mean values of parameters from different methods were compared in different grades of lesions. RESULTS: Our results indicate that the image processing method can change statistical comparisons between different groups for each parameter. The D value is the only quantity in this technique that does not depend on the fitting process and can be used as an indicator of comparison between studies (P < 0.05). The most effective method to distinguish liver lesions is the extrapolated f method (first method). This method created a significant difference (P < 0.05) between the perfusion parameters between benign and malignant lesions. CONCLUSION: Using extrapolated f is the most effective method of distinguishing liver lesions using IVIM parameters. The comparison between groups does not depend on the fitting method only for parameter D.

Triptorelin Peptide Conjugated Alginate Coated Gold Nanoparticles as A New Contrast Media for Targeted Computed Tomography Imaging of Cancer Cells.

OBJECTIVE: Increasing research has been focused on the development of various nanocomplexes as targeted contrast media in diagnostic modalities, mainly in computed tomography (CT) scan imaging. Herein, we report a new method that uses Triptorelin [a luteinizing hormone-releasing hormone (LHRH) agonist]-targeted gold nanoparticles (AuNPs) via alginate for early detection of cancer by molecular CT imaging. MATERIALS AND METHODS: In the experimental study, the formed multifunctional AuNPs coated with alginate conjugated with Triptorelin peptide (Triptorelin-Alginate-AuNPs) were synthesized and characterized via different techniques, including transmission electron microscopy (TEM), dynamic light scattering (DLS), and fourier transform infrared (FTIR) spectroscopy. The MTT assay was applied to calculate the toxicity of the NPs. RESULTS: The results indicated that the formed Triptorelin-Alginate-AuNPs with an Au core size of ~18 nm are noncytotoxic at 127-, 254-, 381- and 508-mM concentrations and revealed significant improvement in the attenuation of X-rays intensity and contrast to noise ratio (CNR), compared with non-targeted cells at the highest energies (90, 120, 140 kVp). At 90 kVp, compared to non-targeted cells, targeted cells (Triptorelin-Alginate-AuNPs) enable 1.58, 1.69, 3.7 and 3.43 times greater contrast at a concentration of 127 mM, 254 mM, 381 mM, and 508 mM, respectively. CONCLUSION: These results suggest that the developed Triptorelin-Alginate-AuNPs may be considered an effective contrast agent for molecular CT imaging of gonadotropin-releasing hormone (GnRH) receptor-expressing cancer cells.

Evaluation of Two Post-Processing Analysis Methods of Proton Magnetic Resonance Spectroscopy in Glioma Tumors.

Background: Magnetic resonance spectroscopy (MRS) is a non-invasive diagnostic and the neuroimaging method of choice for the noninvasive monitoring of brain metabolism in patients with glioma tumors. 1H-MRS is a reliable and non-invasive tool used to study glioma. However, the metabolite spectra obtained by 1H-MRS requires a specific quantification procedure for post-processing. According to our knowledge, no comparisons have yet been made between spectrum analysis software for quantification of gliomas metabolites. Objective: Current study aims to evaluate the difference between this two common software in quantifying cerebral metabolites. Material and Methods: In this analytical study, we evaluate two post-processing software packages, java-based graphical for MR user interface packages (jMRUI) and totally automatic robust quantitation in NMR (TARQUIN) software. 1H-MRS spectrum from the brain of patients with gliomas tumors was collected for post-processing. AMARES algorithms were conducted to metabolite qualification on jMRUI software, and TARQUIN software were implemented with automated quantification algorithms. The study included a total of 30 subjects. For quantification, subjects were divided into a normal group (n=15) and group of gliomas (n=15). Results: When calculated by TARQUIN, the mean metabolites ratio was typically lower than by jMRUI. While, the mean ratio of metabolites varied when quantified by jMRUI vs. TARQUIN, both methods apparent clinical associations. Conclusion: TARQUIN and jMRUI are feasible choices for the post-processing of cerebral MRS data obtained from glioma tumors.

Modified Bismuth Nanoparticles: A New Targeted Nanoprobe for Computed Tomography Imaging of Cancer.

OBJECTIVE: Recently, development of multifunctional contrast agent for effective targeted molecular computed tomography (CT) imaging of cancer cells stays a major problem. In this study, we explain the ability of Triptorelin peptide-targeted multifunctional bismuth nanoparticles (Bi2S3@ BSA-Triptorelin NPs) for molecular CT imaging. MATERIALS AND METHODS: In this experimental study, the formed nanocomplex of Bi2S3@ BSA-Triptorelin NPs was characterized using different methods. The MTT cytotoxicity test was performed to determine the appropriate concentration of nanoparticles in the MCF-7 cells. The X-ray attenuation intensity and Contrast to Noise Ratio (CNR) of targeted and non-targeted nanoparticles were measured at the concentrations of 25, 50, and 75 µg/ml and X-ray tube voltages of 90, 120 and 140 kVp. RESULTS: We showed that the formed Bi2S3@ BSA-Triptorelin NPs with a Bi core size of approximately ~8.6 nm are nontoxic in a given concentration (0-200 µg/ml). At 90, 120, and 140 tube potentials (kVp), the X-ray attenuation of targeted cells were 1.35, 1.36, and 1.33-times, respectively, more than non-targeted MCF-7cells at the concentration of 75 µg/ml. The CNR values at 90, 120, and 140 kVp tube potentials were 171.5, 153.8 and 146.3 c/Ï­, respectively. CONCLUSION: These findings propose that the diagnostic nanocomplex of Bi2S3@ BSA-Triptorelin NPs can be applied as a good contrast medium for molecular CT techniques.

Hyaluronic acid-coated ultrasmall BiOI nanoparticles as a potentially targeted contrast agent for X-ray computed tomography.

Commercial X-ray computed tomography (CT) contrast agents (CAs) are not appropriate for multicolor CT imaging and are limited due to a lack of tumor targeting. In this contribution, to favor the combination of high Z elements like bismuth and iodine for a broad range of X-ray photon energy, BiOI nanoparticles (NPs) are synthesized with hyaluronic acid (HA) coating to target the tumor cells with CD44 overexpression. The crystal structure of BiOI NPs is determined by X-ray powder diffraction, and the size of NPs is determined by a transmission electron microscope at about 14 ± 3 nm. The dynamic diameter of the NPs (DLS) in PBS buffer was measured at about 100 nm. Fourier transform infrared spectroscopy and thermal gravimetric analysis confirm the coating of BiOI NPs with HA. The stability of the NPs was also investigated via UV-vis spectroscopy. The immunocytochemistry process is performed to investigate the targeting ability of synthesized NPs on the human colon cancer cells with CD44 antigen. Finally, the X-ray attenuation of prepared HA-coated BiOI NPs is higher than Iohexol as the commercially available iodinated contrasting agent at the same concentrations, which can be administrated at much lower doses to achieve similar contrast to Iohexol.

Monitoring of the choline/lipid ratio by 1H-MRS can be helpful for prediction and early detection of tumor response to nano-photo-thermal therapy.

Nanotechnology-based photothermal therapy (NPTT) is a new emerging modality of cancer therapy. To have the right prediction and early detection of response to NPTT, it is necessary to get rapid feedback from a tumor treated by NPTT procedure and stay informed of what happens in the tumor site. We performed this study to find if proton magnetic resonance spectroscopy (1H-MRS) can be well responsive to such an imperative requirement. We considered various treatment groups including gold nanoparticles (AuNPs), laser, and the combination of AuNPs and laser (NPTT group). Therapeutic effects on CT26 colon tumor-bearing BALB/c mice were studied by looking at alterations that happened in 1H-MRS signals and tumor size after conducting treatment procedures. In MRS studies, the alterations of choline and lipid concentrations and their ratio were investigated. Having normalized the metabolite peak to water peak, we found a significant decrease in choline concentration post-NPTT (from (1.25 ± 0.05) × 10-3 to (0.43 ± 0.04) × 10-3), while the level of lipid concentration in the tumor was slightly increased (from (2.91 ± 0.23) × 10-3 to (3.52 ± 0.31) × 10-3). As a result, the choline/lipid ratio was significantly decreased post-NPTT (from 0.41 ± 0.11 to 0.11 ± 0.02). Such alterations appeared just 1 day after NPTT. Tumor shrinkage in all groups was studied and significant changes were significantly detectable on day 7 post-NPTT procedure. In conclusion, the study of choline/lipid ratio using 1H-MRS may help us estimate what happens in a tumor treated by the NPTT method. Such an in vivo assessment is interestingly feasible as soon as just 1 day post-NPTT. This would undoubtedly help the oncologists make a more precise decision about treatment planning strategies. Monitoring of the choline/lipid ratio by 1H-MRS can be helpful for prediction and early detection of response to nano-photo-thermal therapy.

Investigation of Specific Targeting of Triptorelin-Conjugated Dextran-Coated Magnetite Nanoparticles as a Targeted Probe in GnRH+ Cancer Cells in MRI.

In recent years, the conjugation of superparamagnetic iron oxide nanoparticles (SPIONs), as tumor-imaging probes for magnetic resonance imaging (MRI), with tumor targeting peptides possesses promising advantages for specific delivery of MRI agents. The objective of the current study was to design a targeted contrast agent for MRI based on Fe3O4 nanoparticles conjugated triptorelin (SPION@triptorelin), which has a great affinity to the GnRH receptors. The SPIONs-coated carboxymethyl dextran (SPION@CMD) conjugated triptorelin (SPION@CMD@triptorelin) were synthesized using coprecipitation method and characterized by DLS, TEM, XRD, FTIR, Zeta, and VSM techniques. The relaxivities of synthetized formulations were then calculated using a 1.5 Tesla clinical magnetic field. MRI, quantitative cellular uptake, and cytotoxicity level of them were estimated. The characterization results confirmed that the formation of SPION@CMD@triptorelin has been conjugated with a suitable size. Our results demonstrated the lack of cellular cytotoxicity of SPION@CMD@triptorelin, and it could increase the cellular uptake of SPIONs to MDA-MB-231 cancer cells 6.50-fold greater than to SPION@CMD at the concentration of 75 µM. The relaxivity calculations for SPION@CMD@triptorelin showed a suitable r 2 and r 2/r 1 with values of 31.75 mM-1·s-1 and 10.26, respectively. Our findings confirm that triptorelin-targeted SPIONs could provide a T 2-weighted probe contrast agent that has the great potential for the diagnosis of GnRH-positive cancer in MRI.

Assessment of some factors of cellular and humoral immunity in radiology workers.

Radiation workers in medical diagnostic departments are occupationally exposed to long-term low-dose ionizing radiation, which may cause radiation-induced side effects. This study investigated subtypes of peripheral blood lymphocytes and immunoglobulin levels in workers who were occupationally exposed to X-ray radiation at the Department of Radiology. Seventeen radiology workers received low levels of ionizing radiation as the study group and 18 individuals who were not exposed to radiation were included as the control group. The percentage of lymphocyte subtypes (CD4+, CD8+ and CD4+/CD8+) and serum levels of immunoglobulins (IgA, IgG and IgM) were measured using peripheral blood samples. Considering all lymphocyte subtypes and serum levels of IgA, IgG and IgM, there was no significant difference between the study and control groups (P > 0.05). There were no significant differences in all mentioned parameters regarding gender (P > 0.05). For the length of employment period, there was a significant difference concerning CD4+/CD8+ (P < 0.05). The findings showed that exposure to low levels of ionizing radiation does not affect the immune system of workers in diagnostic radiology dose level. Because of relatively small samples of workers, it is suggested that these factors be investigated on larger samples of radiology workers.

1H-MRS application in the evaluation of response to photo-thermal therapy using iron oxide-gold core-shell nanoparticles, an in vivo study.

BACKGROUND: Photo-thermal therapy (PTT) has been at the center of attention as a new method for cancer treatment in recent years. It is important to predict the response to treatment in the PTT procedure. Using magnetic resonance spectroscopy (MRS) can be considered a novel technique in evaluating changes in metabolites resulted from PTT. METHODS: In the present project, we conducted an in vivo study to assess the efficacy of 1H-MRS as a noninvasive technique to evaluate the response to treatment in the early hours following PTT. The BALB/c mice subcutaneously bearing tumor cells (CT26 cell line) were scanned by 1H-MRS before and after PTT. Iron oxide-gold core-shell (Fe3O4@Au) as PTT agent was injected into intra-peritoneal at first and then irradiated by NIR laser. Single-voxel Point RESolved Spectroscopy (PRESS) sequence (TE = 144) was used, and metabolites alternations were evaluated by the non-parametric Wilcoxon test. Besides, Nanoparticle (NP) relaxometry was conducted for negative contrast agents' potentials. RESULTS: MRS choline (Cho) peak dramatically reduced 24 h post-PTT (p = 0.01) and lipid peak as a marker for necrosis of tumor elevated (p = 0.01) just in group 3 (NPs injection + laser irradiation) 24 h after the procedure. CONCLUSION: 1H-MRS showed its potential as a method in detecting the changes in metabolites and revealing the outcome accurately. Response to photo-thermal therapy evaluation was achievable only one day after PTT and proved by a 10-day follow-up of the tumor size. Iron oxide-gold core-shell can also be used as a negative contrast agent in MRI images during therapy.

Superparamagnetic cobalt ferrite nanoparticles as T2 contrast agent in MRI: in vitro study.

Superparamagnetic cobalt ferrite nanoparticles (CoFe2O4) possess favourite advantages for theranostic applications. Most of previous studies reported that CoFe2O4 magnetic nanoparticles (MNPs) are suitable candidates for induction of hyperthermia and transfection agents for drug delivery. The present study synthesized and investigated the potential use of CoFe2O4 as a contrast agent in magnetic resonance imaging (MRI) by using a conventional MRI system. The CoFe2O4 were synthesized using co-precipitation method and characterized by TEM, XRD, FTIR, EDX and VSM techniques. Relaxivities r1 and r2 of CoFe2O4 were then calculated using a 1.5 Tesla clinical magnetic field. The cytotoxicity of CoFe2O4 was evaluated by the MTT assay. Finally, the optimal concentrations of MNPs for MRI uses were calculated through the analysis of T2 weighted imaging cell phantoms. The superparamagnetic CoFe2O4 NPs with an average stable size of 10.45 nm were synthesized. Relaxivity r1,2 calculations resulted in suitable r2 and r2/ r1 with values of 58.6 and 51 that confirmed the size dependency on relaxivity values. The optimal concentration of MNPs for MR image acquisition was calculated as 0.154 mM. Conclusion: CoFe2O4 synthesized in this study could be considered as a suitable T2 weighted contrast agent because of its high r2/r1 value.

Neurochemical metabolite alterations of the occipital lobe in migraine without aura by proton magnetic resonance spectroscopy.

BACKGROUND: Migraine without aura is the most common type of migraine headache, accounting for about 80% of all migraines. The aim of the present investigation was to determine the neurochemical metabolite alterations in the occipital lobe of patients suffering from migraine without aura using proton magnetic resonance spectroscopy (1H-MRS). METHODS: Fifteen patients suffering from migraine without aura with an occipital plaque and 16 healthy controls were included in this study. Changes in the neurochemical metabolites in the occipital lobe were assessed using 1H-MRS. The ratios of N-acetylaspartate (NAA) to creatine (Cr), choline (Cho) to Cr and myo-inositol (MI) to NAA were measured by voxel volume at 8 cm3. RESULTS: The mean NAA/Cr ratio decreased significantly in patients compared to controls. Cho/Cr and MI/NAA ratios increased significantly in patients. In addition, the duration of the disease and the frequency of headache attacks were significantly associated with a decrease in the NAA/Cr ratio and an increase in the Cho/Cr ratio. CONCLUSIONS: Migraine without aura shows a significant association with changes in neurochemical metabolites detectable by 1H-MRS in the occipital lobe of patients. In addition, changes in metabolic ratios showed a significant relationship with the duration of the disease and the frequency of headache attacks.

Investigation of combined photodynamic and radiotherapy effects of gallium phthalocyanine chloride on MCF-7 breast cancer cells.

In this study, we evaluated the effect of gallium phthalocyanine chloride (GaPcCl) as a radio- and photosensitizer on MCF-7 breast cancer cell line. We incubated cells with GaPcCl in different concentrations (from 3.125 to 100 µg/ml). Then cells in separate groups were exposed to different light doses (1.8 and 2.8 J/cm2) at wavelength of 660 nm and 2-Gy X-ray ionizing radiation, alone and in combination. Finally, cell survival and apoptosis were determined by MTT assay and flow cytometry, respectively. The results showed that the deactivated GaPcCl at concentration of 100 µg/ml reduces the cell viability up to 15%. While, photoactivated GaPcCl (100 µg/ml) at light dose of 2.8 J/cm2 significantly decreases cell viability up to 55.3%. Although MTT assay demonstrated that GaPcCl is not act as a radiosensitizer, flow cytometry showed significant increase in cell apoptosis when GaPcCl was exposed to 2 Gy X-ray. Using of GaPcCl-PDT (photodynamic therapy) integration with X-ray substantially increased cell death in comparison to the absence of X-ray. Furthermore, flow cytometry displayed a significant increase in apoptosis cells (especially late apoptosis) in this combination therapy. Our result proved that GaPcCl is an effective photosensitizer in MCF-7 human breast cancer cell line. The combination of GaPcCl-PDT and radiotherapy can be an efficient treatment against cancer. This approach needs further investigations on animal models for human purposes.Graphic abstract.

Folate-modified and curcumin-loaded dendritic magnetite nanocarriers for the targeted thermo-chemotherapy of cancer cells.

A novel multifunctional nanoplatform constructed from methoxy-PEGylated poly(amidoamine) (PAMAM) generation 3 dendrimers with superparamagnetic iron oxide nanoparticles (SPIONs) entrapped in their core, containing curcumin as the payload drug and folic acid (folate) as the targeting ligand (abbreviated as FA-mPEG-PAMAM G3-CUR@SPIONs), is presented in this study. SPIONs entrapped in the core of the nanocomplex may act as a hyperthermia agent and generate localized heat upon excitation with an alternating magnetic field (AMF), thus enabling a thermo-chemotherapy strategy for cancer treatment. Accordingly, the cytotoxic effect and the mode of cell death triggered by the nanocomplex in combination with AMF were evaluated on two different cancer cell lines with various folate receptor (FR) expression levels, including KB nasopharyngeal cancer cells overexpressing FRs as the model and MCF-7 breast cancer cells with low level of FRs as the blank sample. The obtained results showed that KB cell death was greater than the cell death observed in MCF-7 cells. Moreover, a majority of cell death in both cell lines were related to apoptosis when the folate-modified nanocomplex was used instated of the non-folate-modified nanocomplex. Therefore, functionalizing the nanocomplex with folate modulated the response to thermo-chemotherapy by shifting the cell death pathways toward apoptosis.

The benefits of folic acid-modified gold nanoparticles in CT-based molecular imaging: radiation dose reduction and image contrast enhancement.

X-ray computed tomography (CT) requires an optimal compromise between image quality and patient dose. While high image quality is an important requirement in CT, the radiation dose must be kept minimal to protect the patients from ionizing radiation-associated risks. The use of probes based on gold nanoparticles (AuNPs) along with active targeting ligands for specific recognition of cancer cells may be one of the balanced solutions. Herein, we report the effect of folic acid (FA)-modified AuNP as a targeted nanoprobe on the contrast enhancement of CT images as well as its potential for patient dose reduction. For this purpose, nasopharyngeal KB cancer cells overexpressing FA receptors were incubated with AuNPs with and without FA modification and imaged in a CT scanner with the following X-ray tube parameters: peak tube voltage of 130 KVp, and tube current-time products of 60, 90, 120, 160 and 250 mAs. Moreover, in order to estimate the radiation dose to which the patient was exposed during a head CT protocol, the CT dose index (CTDI) value was measured by an X-ray electrometer by changing the tube current-time product. Raising the tube current-time product from 60 to 250 mAs significantly increased the absorbed dose from 18 mGy to 75 mGy. This increase was not associated with a significant enhancement of the image quality of the KB cells. However, an obvious increase in image brightness and CT signal intensity (quantified by Hounsfield units [HU]) were observed in cells exposed to nanoparticles without any increase in the mAs product or radiation dose. Under the same Au concentration, KB cells exposed to FA-modified AuNPs had significantly higher HU and brighter CT images than those of the cells exposed to AuNPs without FA modification. In conclusion, FA-modified AuNP can be considered as a targeted CT nanoprobe with the potential for dose reduction by keeping the required mAs product as low as possible while enhancing image contrast.

Folic acid conjugated PEG coated gold-iron oxide core-shell nanocomplex as a potential agent for targeted photothermal therapy of cancer.

This study reports the synthesis and characterization of poly(ethylene glycol) coated gold@iron oxide core-shell nanoparticles conjugated with folic acid (FA-PEG-Au@IONP). Also, targeted therapeutic properties of such a nanocomplex were studied on human nasopharyngeal carcinoma cell line KB and human breast adenocarcinoma cell line MCF-7 in vitro. The synthesized nanocomplex was characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), UV-Vis spectroscopy, vibrating sample magnetometry (VSM), and Fourier transform infrared (FTIR) spectroscopy. The photothermal effects of nanocomplex on both KB and MCF-7 cell lines were studied. Cell death and apoptosis were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry using an annexin V-fluorescein isothiocyanate/propidiumiodide apoptosis detection kit. It was found that nanocomplex is spherical in shape and its size is approximately 60 nm. UV-vis spectrum showed that nanocomplex has appropriate absorption near infrared region. FTIR spectra obtained from nanocomplex before and after conjugation with FA confirmed the formation of folate conjugated nanocomplex. Significant cell lethality was observed for KB (∼62%) and MCF-7 (∼33%) cells following photothermal therapy. Also, it was found that majority of the cell deaths were related to apoptosis process. It can be concluded that, the synthesized nanocomplex is an effective and promising multifunctional nanoplatform for targeted photothermal therapy of cancer.

Mitoxantrone as a prospective photosensitizer for photodynamic therapy of breast cancer.

Photodynamic therapy has the potential to become an effective alternate to surgery for the treatment of cancer. In recent years, there has been a focus on identifying more effective and less toxic photosentisizers for use in photodynamic therapy. The purpose of this study was to assess the effectiveness of mitoxantrone, a chemotherapeutic agent, as a photosensitizer for photodynamic therapy in the MCF-7 human breast cancer cell line. Cytotoxicity was evaluated for different concentrations of mitoxantrone, and photosensitivity was assessed using a non-coherent light source. The percentage of the cell survival after 24 h was investigated using the MTT assay. Overall, the results showed that mitoxantrone is a remarkably efficient photosensitizer that could mediate MCF-7 cell death at a low concentration (5 µM) with modest exposure to light. It is surprising to find that a chemotherapeutic agent can be an effective photosensitizer for PDT in vitro.