Estimating the skin dose near to the applicator and acute toxicity in breast cancer patients: An intraoperative electron radiotherapy technique.

Introduction: Intraoperative electron radiation therapy (IOERT) is one of the most recently popular therapeutic methods for breast cancer. This study aimed to measure the skin dose near the applicator during IOERT of breast cancer patients, as well as, the incidence of acute toxicity after surgery. Materials and Methods: Thirty-six female patients participated in the current study with the prescribed dose of 21 and 12 Gy for IOERT as full and boost, respectively. The skin dose was investigated based on different applicator sizes, tumor bed thicknesses, and monitor units (MUs). The energy was chosen 8 MeV, and EBT3 film was used for the dosimetric process. In addition, the acute toxicity included healing time for the surgical wound, scaling of the skin, itching, necrosis, redness as well as seroma formation for 1 week and 1 month were recorded. The results were compared to those of 22 patients who underwent the surgery without IOERT. Results: The highest skin dose for the patients was obtained 2.09 Gy, which is lower than the threshold dose (6 Gy). Furthermore, the findings showed that the average skin dose was higher in bigger applicator sizes and MU and lower tumor bed thicknesses. The average of wound healing for the patient underwent IOERT and without the use of IOERT (as the control group) was 19.32 and 11.67 days, respectively. One month after surgery, the volume of aspirated seroma was higher in the patients who performed IOERT compared to the control group (250 ml vs. 200 ml). It is notable that there were not observed any redness, itching, scaling, and necrosis in both investigated groups. Conclusion: Owing to the results, the skin dose during IOERT was lower than the recommended level. The dose of IOERT as a full was higher than boost which can be related to the lower number of the patients in full method; however, there was a well-tolerated without severe acute complication, especially seroma formation and wound healing time in both full and boost methods.

Clinical Breast Cancer Registry of IR. Iran (CBCR-IR): Study Protocol and First Results.

BACKGROUND: Breast cancer (BC), as a significant global health problem, is the most common cancer in women. Despite the importance of clinical cancer registries in improving the quality of cancer care and cancer research, there are few reports on them from low- and middle-income countries. We established a multicenter clinical breast cancer registry in Iran (CBCR-IR) to collect data on BC cases, the pattern of care, and the quality-of-care indicators in different hospitals across the country. METHODS: We established a clinical cancer registry in 12 provinces of Iran. We defined the organizational structure, developed minimal data sets and data dictionaries, verified data sources and registration processes, and developed the necessary registry software. During this registry, we studied the clinical characteristics and outcomes of patients with cancer who were admitted from 2014 onwards. RESULTS: We registered 13086 BC cases (7874 eligible cases) between 1.1.2014 and 1.1.2022. Core needle biopsy from the tumor (61.25%) and diagnostic mammography (68.78%) were the two most commonly used diagnostic methods. Stage distribution was 2.03% carcinoma in situ, 12% stage I, 44.65% stage II, 21.32% stage III, and 4.61% stage IV; stage information was missing in 1532 patients (19.46%). Surgery (95.01%) and chemotherapy (79.65%) were the most common treatments for all patients. CONCLUSION: The information provided by this registry can be used to evaluate and improve the quality of care for BC patients. It will be scaled up to the national level as an important resource for measuring quality of care and conducting clinical cancer research in Iran.

Novel manganese carbon quantum dots as a nano-probe: Facile synthesis, characterization and their application in naproxen delivery (Mn/CQD/SiO2@naproxen).

This study for the first time pursues two crucial aims of using Naproxen as a non-steroidal anti-inflammatory drug in a better, non-invasive setting and introducing a simple and biocompatible nano-carrier (Mn/CQD/SiO2) which is a magneto carbon quantum dots modified with mesoporous silica probe which can be served as a drug delivery and tracer system. SiO2modification was doneby mesoporous silica which improves biocompatibility and provideslow cytotoxicity. Naproxen was conjugated to the nano-probe to form Mn/CQD/SiO2@naproxen and biodistribution was investigated. Physicochemical characteristics of the Mn/CQD/SiO2@naproxen were investigated using FT-IR, SEM, TEM, UV-Vis and BET. Antiproliferation assay using MTT assay was performed on HEK-293 cells to determine the cytotoxity of Mn/CQD/SiO2@naproxen. Relaxivity of Mn/CQD/SiO2 was examined thereafter. To investigate the imaging capability of Mn/CQD/SiO2@naproxen and biodistribution of Naproxen, fluorescent imaging was done. To confirm the data, then the levels of COX Gene expression was determined. The specific surface area, pore volume, and pore radius were 44.4 m2/g, 10.23 cm3/g, and 25.9 nm respectively. MTT assay showed no cytotoxicity. Relaxivity of Mn/CQD/SiO2 was higher than conventional Gd-based contrast agent. Fluorescence imaging of Mn/CQD/SiO2@naproxen showed the biodistribution of naproxen. COX Gene expression confirmed the biodistribution data. By increasing the accumulation in liver COX production reduced. All in all, unique features of Mn/CQD/SiO2 including biocompatibility, low toxicity, magnetic and fluorescence properties showed that it can be used in biomedical sciences.

Therapeutic effect of cold atmospheric plasma and its combination with radiation as a novel approach on inhibiting cervical cancer cell growth (HeLa cells).

Cervical cancer is one of the important cancers in women. Research on novel treatment approach can reduce the mortality and burden. Although radiotherapy is a common treatment, its negative side effects have concerned physician. In our study, we studied impact of cold atmospheric pressure plasma on the Hela cancer cells, as an alternative treatment. The effect of three different types of such plasma; dielectric barrier discharge (DBD), plasma jet, and afterglow plasma, on the cancer cells were studied. Moreover, some effective operating parameters such as exposure time, applied voltage, composition of working gas in plasma treatment were investigated on the survival of the afterglow plasma. Finally, treatments by the afterglow plasma, gamma radiation (1 Gy), and combination of both were compared. Analysis showed that DBD and plasma jet (direct exposure) effectively killed the cancer cells, even by a minimum applied voltage. But a fraction of the cells survived after the exposure of indirect diffused afterglow plasma. In the case of this plasma, we realized that higher applied voltage and exposure time led to less cell viability. Fewer fractions of survival cells were detected in the case of argon afterglow plasma comparing to oxygen afterglow. Cold atmospheric plasma and its combination with radiation therapy showed a significant decrease in viability of the cells, comparing to the radiation alone. Our research showed that plasma and its combination with radiation therapy have superiority over radiation therapy.

Enhanced catalytic and antibacterial efficiency of biosynthesized Convolvulus fruticosus extract capped gold nanoparticles (CFE@AuNPs).

Scientists are interested in biosynthesis of gold nanoparticles owing to their catalytic and biological features. In this research, the extract of Convolvulus fruticosus (C. fruticosus; CFE) extract was applied to synthesize spherical-like gold nanoparticles (CFE@AuNPs). As-prepared CFE@AuNPs was characterized by TEM, FE-SEM, XRD, FT-IR, EDS, UV-Vis and DLS analysis. Identification analysis revealed that the properties of as-prepared CFE@AuNPs with spherical morphology were homogeneous, regular, high dispersibility and low agglomeration. The particle size of biogenic gold nanoparticles (about 35 nm) was obtained using FE-SEM, TEM and DLS techniques. Photocatalytic experiment of CFE@AuNPs determined by degradation of basic violet 10 (BV10), basic blue 9 (BB9) and acid red 51 (AR51) pollutants with percent degradation of 94.3%, 90.2%, 85.4% under UV and 80.6%, 79.8%, 73.3% under visible light irradiation, respectively. As well as, as-prepared CFE@AuNPs illustrated as a significant inhibitory influence against ATCC strain for both gram-positive and gram-negative bacteria. Owing to the antibacterial results, CFE@AuNPs enhanced antibacterial activity against E. coli, A. baumannii, P. aeruginosa, S. aureus, K. pneumonia, P. mirabilis and E. faecalis with MIC of 0.075, 0.075, 0.075, 0.075, 0.15, 0.075 and 0.037 mg/ml, respectively. All in all, results of the findings showed that C. fruticosus capped gold nanoparticles can find applications in the various arena including biological and removal of toxic pollutants for water purification.

Mesopourous Fe3O4@SiO2-hydroxyapatite nanocomposite: Green sonochemical synthesis using strawberry fruit extract as a capping agent, characterization and their application in sulfasalazine delivery and cytotoxicity.

The present study introduces a simple, biocompatible and effective drug delivery system by using mesoporous nanocomposite-based platform. To achieve this goal, mesopourous Fe3O4@SiO2-hydroxyapatite nanocomposite (mFSH) was synthesized by sonochemical process in presence of strawberry fruit extract as capping agent (mFSH-SW). The impact of various factors such as sonication time (5, 15, 30 and 45 min), capping agent (cherry (CH), strawberry (SW), malus domestica (MD), andean blackberry (AB)), pH (10, 11 and 12) and sonication power (30, 60 and 80 W) were investigated to reach optimum condition. To reach high efficiency of drug loading, mFSH was grafted with 3-aminopropyl triethoxysilane (APTES). Uniform, regular and spherical morphology of nanocomposite were specified by field emission scanning electron microscopy (FESEM), X-ray powder diffraction (XRD), vibrating sample magnetometer (VSM), high-resolution transmission electron microscopy (HRTEM), energy-dispersive x-ray spectroscopy (EDX), dynamic light scattering (DLS), nitrogen adsorption/desorption isotherm and Fourier-transform infrared spectroscopy (FT-IR) techniques. The mean pore size, surface area, and pore volume of mFSH-SW were 63.2 m2 g-1, 14.1 nm and 0.24 cm3 g-1, respectively. Sulfasalazine (SLN) loading and release were carried out by various products. The functionalized mFSH-SW showed high adsorption capacity (approximately 59.1 %) for SLN that possesses amino functional groups. The results showed that 100 % of SLN-loaded nanocomposite could be released after 36 h at intestinal conditions (pH = 6.8). In addition, in-vitro and in-vivo toxicity investigations of product were performed with apoptosis/necrosis, XTT and pathology assay, respectively. All in all, unique properties of the nanocomposite including low toxicity, high drug loading, slow release and biodegradable showed that it can be used in biomedical sciences.

Synthesis and characterization of novel 99mTc-DGC nano-complexes for improvement of heart diagnostic.

In this research, early diagnosis of cardiovascular diseases can reduce their mortality and burden. In our study, we developed a new nano-agent, 99mTc-Dendrimer Glyco Conjugate (99mTc-DGC), and assessed its safety and capability for myocardial viability scan. To develop 99mTc-DGC, we first synthesized the dendrimer and then, glucose has been conjugated. Afterwards, we measured toxicity of the product on normal cells by XTT and apoptosis/necrosis methods. We compared the myocardial viability scan (measured by SPECT and dynamic planar imaging) in two rabbit models, with and without infarction. We also assessed the biodistribution of 99mTc-DGC in rats with no infarction. DGC synthesis was confirmed by Fourier transform infrared (FT-IR), proton nuclear magnetic resonance (1H NMR), liquid chromatography-mass spectrometry (LC-MS), dynamic light scattering (DLS) and static light scattering techniques (SLS). Then radiochemical purity (RCP) was done to present the stability and potential of DGC to complex formation with 99mTc. In vitro cytotoxicity showed nontoxic concentration up to 8 mg/mL. Single Photon Emission Computed Tomography (SPECT) and dynamic planar imaging clearly showed the accumulation of 99mTc-DGC in myocardial. Biodistribution result showed the 2.60% accumulation of 99mTc-DGC in myocardial after 2 h. Our findings indicated 99mTc-DGC to be safe and can accurately diagnose myocardial infarctions at early stages. Human studies to further assess such effects are critical.

PEG-Citrate dendrimer second generation: is this a good carrier for imaging agents In Vitro and In Vivo?

While cancer is the leading cause of human's deaths worldwide, finding an imaging agent which can detect cancer tumours is needed for cancer diagnosis. In the present study, PEG-citrate dendrimer-G2 was used as a nano-carrier of FITC dye and Iohexol to help passive targeting and uptake of both imaging agents in cancer cells/tumour in vitro and in vivo. Dendrimer was synthesisedand the product characterised using LC-MS, FT-IR, DLS, ELS, AFM, and 1HNMR. After FITC loading into dendrimer, MTT was performed to determine the cytotoxicity of formulation on HEK-293 and MCF-7 cells. In vitro imaging using dendrimer-FITC was done via fluorescent microscope thereafter. Moreover, CT imaging using Iohexol was employed to show the targeting nature and ability of the complex to use as imaging agent in vivo. Data yielded in this study corroborate the notion that the promised dendrimer was synthesised properly and had no toxicity along with FITC on normal cell. Furthermore, CT and fluorescent images showed the targeting nature and imaging ability of Iohexol/FITC loaded dendrimer in vitro and in vivo. Overall, results showed promising characteristics of the novel complexes using dendrimer-G2 both in vitro and in vivo.

Technetium-99m chelator-free radiolabeling of specific glutamine tumor imaging nanoprobe: in vitro and in vivo evaluations.

INTRODUCTION: Nowadays, molecular imaging radiopharmaceuticals', nanoparticles', and/or small-molecule biomarkers' applications are increasing rapidly worldwide. Thus, researchers focus on providing the novel, safe, and cost-effective ones. MATERIALS AND METHODS: In the present experiment, technetium-99m (99mTc)-labeled PEG-citrate dendrimer-G2 conjugated with glutamine (nanoconjugate) was designed and assessed as a novel tumor imaging probe both in vitro and in vivo. Nanoconjugate was synthesized and the synthesis was confirmed by Fourier transform infrared, proton nuclear magnetic resonance, liquid chromatography-mass spectrometry, dynamic light scattering, and static light scattering techniques. The toxicity was assessed by XTT and apoptosis and necrosis methods. RESULTS: Radiochemical purity indicates that the anionic dendrimer has a very high potential to complex formation with 99mTc and is also very stable in the human serum in different times. Results from the imaging procedures showed potential ability of nanoconjugates to detect tumor site. CONCLUSION: Suitable features of the anionic dendrimer show that it is a promising agent to improve nanoradiopharmaceuticals.

AS1411 Aptamer-Anionic Linear Globular Dendrimer G2-Iohexol Selective Nano-Theranostics.

Molecular theranostics is of the utmost interest for diagnosis as well as treatment of different malignancies. In the present study, anionic linear globular dendrimer G2 is employed as a suitable carrier for delivery and AS1411 aptamer is exploited as the targeting agent to carry Iohexol specifically to the human breast cancer cells (MCF-7). Dendrimer G2 was prepared and conjugation of dendrimer and aptamer was carried out thereafter. Based on the data yielded by AFM, morphology of smooth and spherical non-targeted dendrimer changed to the rough aspherical shape when it conjugated. Then, conjugation was confirmed using DLS, ELS and SLS methods. Toxicity on nucleolin positive MCF-7 cells and nucleolin negative HEK-293 cells was assessed by XTT and apoptosis/necrosis assays. In vitro uptake was determined using DAPI-FITC staining and ICP-MS methods. In vivo studies including in vivo CT imaging, pathology and blood tests were done to confirm the imaging ability, bio-safety and targeted nature of the Nano-Theranostics in vivo. In a nutshell, the prepared construction showed promising effects upon decreasing the toxicity of Iohexol on normal cells and accumulation of it in the cancer tumors as well as reducing the number of cancer cells.

Novel chlorambucil-conjugated anionic linear-globular PEG-based second-generation dendrimer: in vitro/in vivo improved anticancer activity.

Evaluating the efficacy of anticancer drugs is an evolving and research-oriented issue. The objective of this study was to reduce the insolubility of chlorambucil (CBL) in water and improve the anticancer activity of CBL in vitro and in vivo through the conjugation of CBL with anionic linear-globular dendrimer (second generation, G2). In the current study, the anticancer activity among three groups that include CBL, CBL-G2 dendrimer, and control was measured in vitro and in vivo. In vitro studies showed that G2 anionic linear-globular polyethylene-glycol-based dendrimer, which conjugated to the CBL exterior through an ester linkage, was able to significantly improve the treatment efficacy over clinical CBL alone with respect to proliferation assay, 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide; half maximal inhibitory concentration (IC50) was calculated to be 141 µg/mL for CBL alone and 27.7 µg/mL for CBL-G2 dendrimer; P<0.05. In addition, CBL-G2 dendrimer conjugate forestalled the growth of MCF-7 cancerous cells in addition to enhancing the number of apoptotic and necrotic cells as demonstrated by an annexin V-fluorescein isothiocyanate assay. CBL-G2 dendrimer conjugate was able to checkmate antiapoptotic Bcl-2 expression and Bcl-2/Bax ratio in a large scale compared with the control group and CBL alone (P<0.005). In vivo studies showed that tumor treatment by CBL-G2 dendrimer conjugate outstrips the efficacy of treatment compared with CBL alone. The evaluation was based on reduction in tumor volume and tumor growth inhibition of murine 4T1 mammary tumor cells. Tumor volume of 140%±8% was measured in the treatment with CBL-G2 dendrimer, whereas 152%±13.5% was calculated in the treatment with free CBL (P<0.05). However, there were no significant differences in histological assay among the three groups. In conclusion, tumor growth suppression potential of CBL-G2 dendrimer, which was assessed in both in vitro and in vivo experiments, has provided empirical evidence to buttress the fact that this compound could be considered for functional cancer treatment with low side effects.

Synthesis, Characterization, and Atenolol Delivery Application of Functionalized Mesoporous Hydroxyapatite Nanoparticles Prepared by Microwave-Assisted Co-precipitation Method.

BACKGROUND: Atenolol has been used to treat angina and hypertension, either alone or with other antihypertensives. Despite its usefulness, it shows some side effects such as diarrhea and nausea in some patients. A method for slow release of atenolol in intestine is helpful to prevent such side effects. METHODS: A facile co-precipitation microwave-assisted method was used to fabricate mesoporous hydroxyapatite nanoparticles (mHAp). It was then functionalized to have SO3H groups. The synthesized material was used for storage/slow release study of atenolol. RESULTS: Atenolol loaded mHAp shows immediate release of atenolol in pH 8, whileafter functionalizing shows up to ca. 30% release at the beginning. In pH 1, 50% of drug was released after 10 h from AT@mHAp and after 18h the drug was almost completely released.The drug release profiles of functionalized HAp at pH value 1 and 8reveals the complete release of atenolol in intestine pH, while no complete release is observed in stomach environment. CONCLUSION: The aims of this work were synthesis and characterization of mesoporous HAp through the microwave-assisted co-precipitation method and elucidate the underlying drug release capability of mesoporous HAp nanoparticles. The SO3H group was incorporated into the mesoporous HAp and then used as drug delivery carriers using atenolol as a model drug to investigate their drug storage/release properties in simulated body fluid (SBF). Increasing pH value to 8 causes increase in the drug release.