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. © 2017 The Author(s)

99mTc-anionic linear globular dendrimer-G2-phenylalanine conjugate: Novel brain tumor SPECT imaging

The purpose of this study was the investigation of the targeting potential of99mTc-Labeled dendrimer-phenylalanine conjugate for brain tumor SPECT imaging. L-Type amino acid transporters (LAT1) are highly expressed in the blood-brain barrier as well as in brain cancer cells; thus, targeting LAT1 using phenylalanine could improve the sensitivity and specificity of radiosynthesis nanocarrier. In this study, the dendrimer G2�phenylalanine conjugate was synthesized and characterized by Fourier transform infrared spectroscopy, atomic force microscopy, particle size, and zeta potential. MTT assay was done for cell viability measurement in different concentrations of nanoparticles (0.125, 0.25, 0.5 mg/ml) on C6 glioma cell lines; the uptake study was evaluated using fluorescence-activated cell sorter (FACS) instrument; finally, SPECT scintigraphy in glioma tumor-bearing Wistar rats was done. The dendrimer-phenylalanine conjugate particle size was found in the range of 74.14±2.2 to 109±3.1 nm, with a slightly negative surface charge. Also, phenylalanine present on the dendrimer's surface� phenylalanine conjugate enhanced the dendrimer's cellular uptake�phenylalanine conjugate on the C6 glioma cell line. Results of SPECT imaging and fluorescence studies revealed that dendrimer� phenylalanine conjugate accumulated into the brain tumor cells, and it can be suggested as a promising brain-targeting probe with no toxicity in brain tumor imaging. © 2020 by the authors

Preparation and Evaluation of a New Lipopolysaccharide-based Conjugate as a Vaccine Candidate for Brucellosis

Objectives: Development of an efficacious vaccine against brucellosis has been a challenge for scientists for many years. At present, there is no licensed vaccine against human brucellosis. To overcome this problem, currently, antigenic determinants of Brucella cell wall such as Lipopolysaccharide (LPS) are considered as potential candidates to develop subunit vaccines. Methods: In this study, Brucella abortus LPS was used for conjugation to Neisseria meningitidis serogroup B outer membrane vesicle (OMV) as carrier protein using carbodiimide and adipic acid-mediated coupling and linking, respectively. Groups of eight BALB/c mice were injected subcutaneously with 10μg LPS alone, combined LPS+OMV and conjugated LPS-OMV on 0 days, 14 days, 28 days and 42 days. Anti-LPS IgG was measured in serum. Results: The yield of LPS to OMV in LPS-OMV conjugate was 46.55, on the basis of carbohydrate content. The ratio for LPS to OMV was 4.07. The LPS-OMV conjugate was the most immunogenic compound that stimulated following the first injection with increased IgG titer of ~5-fold and ~1.3-fold higher than that produced against LPS and LPS in noncovalent complex to OMV (LPS+OMV), respectively. The highest anti-LPS IgG titer was detected 2 weeks after the third injection (Day 42) of LPS-OMV conjugate. The conjugated compound elicited higher titers of IgG than LPS+OMV, that showed a 100-120-fold rise of anti-LPS IgG in mice. Conclusion: These results indicate that our conjugated LPS-OMV can be used as a brucellosis vaccine, but further investigation is required. © 2014

Breast cancer cells imaging by targeting methionine transporters with gadolinium-based nanoprobe

Purpose: Early cancer diagnosis using MRI imaging is of high global interest as a non-invasive and powerful modality. In this study, methionine was conjugated on gadolinium-based mesoporous silica nanospheres to evaluate intra-cellular uptake and its accumulation in human breast cancer cells. Procedures: The contrast agent was synthesized and characterized using different techniques including N2 physisorption, thermal gravimetric analysis, dynamic light scattering, and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The intra-cellular uptake of Gd3+ was measured by ICP-AES, fluorescent microscopy, and flow cytometry. Finally, cellular and tumor MR imaging were performed to determine in vitro and in vivo relaxometry. Results: According to the results, the contrast agents accumulated in tumor cells both in vitro and in vivo. There was no significant cellular toxicity on either normal or cancer cells along with strong intense signal on T1 compared to the unlabeled cells. Conclusions: The results showed that the novel contrast agent could become a useful tool in early detection of cancer. © 2014 World Molecular Imaging Society

The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019

BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden

Inverse Method to Estimate the Mass of Contamination Source by Comparing Analytical with Numerical Results

The development of a conceptual model that best accounts for the different parameters influencing LNAPL fate and transport in groundwater is ultimate the key to a successful simulation of LNAPL concentration in groundwater. Characterization of hydrocarbon sources and identification of areas with heavy LNAPL loadings from point and non-point sources is important for land use planners and environmental regulators.Bistoon petrochemical site has discharged the light nonaqueous phase liquid (LNAPL) contamination for 10 months. Since the amount of contamination in this source is not clear and the only available data is the amount of contamination in the observed well, an attempt was made to solve this problem by using inverse method. The amount of source contaminant was found through observed data in the well. In this method the analytical results with numerical ones were compared. Upon computation of the contamination concentration, the mass of contaminants can be calculated by multiplying concentration by volume. The numerical method used is finite difference which is an engine in Modflow program

In Vitro Evaluation of Gd3+-Anionic Linear Globular Dendrimer-Monoclonal Antibody: Potential Magnetic Resonance Imaging Contrast Agents for Prostate Cancer Cell Imaging

Purpose: Early stage prostate cancer diagnosis is of high global interest. Magnetic resonance imaging (MRI) is a non-invasive modality for early cancer diagnosis, in particular for prostate cancer detection. The research aim is to synthesize a nanodendrimer and its conjugate with C595 monoclonal antibody (mAb C595), against prostate cancer, followed by its chelating with Gd3+. Procedures: Anti-MUC-1 mAb C595 was conjugated to an anionic linear globular dendrimer (ALGDG2). The polyethylene glycol core and citric acid shell were synthesized followed by loading with Gd3+ to make novel contrast agents for functional MRI. The in vitro behavior and MRI parameters of the nanoconjugate were investigated performing several studies such as cell toxicity and TNF-alpha evaluations. The investigation of magnetic resonance imaging parameters indicated how well nanoconjugate performs in 1H-NMR and 17O-NMR in vitro. Results: Results showed a potential specific MRI activity by improving the swelling responses cell binding. The MTT (2-(4,5-dimethyl-2-thiazolyl)-3,5-diphenyl-2H-tetrazolium bromide) assay demonstrated that this contrast agent had significant cytotoxicity on prostate cancer cells. Conclusions: These results showed that Gd3+-ALGDG2-C595 is a potential prostate molecular imaging agent and could be considered as an ideal functional nanoprobe. Additionally, further investigations by clinical trials are in the pipeline. © 2015, World Molecular Imaging Society

Technetium-99 m-PEGylated dendrimer-G2-(Dabcyle-Lys6,Phe7)-pHBSP: A novel Nano-Radiotracer for molecular and early detecting of cardiac ischemic region

In cardiac ischemic disorder, pyroglutamate helix B surface peptide (pHBSP) which derived from erythropoietin causes to increase cell stability. To improve the serum stability of pHBSP, two lipophilic amino acids Arg6, Ala7 were replaced with Fmoc-(Dabcyle)-Lys-OH and Fmoc-Phe-OH during the peptide synthesis. This peptide was subsequently conjugated to PEGylated dendrimer-G2 and labeled with 99mTcO4 � to detect cardiac ischemic region. Radiochemical purity (RCP) of 99mTc-PEGylated dendrimer-G2-(Dabcyle-Lys6,Phe7)-pHBSP was evaluated by ITLC method. In addition, the radiopeptide was investigated for stability in human serum and binding affinity to hypoxic cells in myocardium H9c2 cell lines. Biodistribution and SPECT/CT scintigraphy were assessed in cardiac ischemic rats. Radiochemical yield indicated that the anionic dendrimer has a very high potential to complex formation with 99mTcO� 4 (RCP > 94) which was stable in human serum with RCP 89 up to 6 h. The binding of 99mTc- nanoconjugate to hypoxic cells was significantly more than normoxic cells (3-fold higher compared to normoxic cells at 1 h). In biodistribution studies, erythropoietin receptor-Beta common receptor (EPO-BcR)-positive uptake in the cardiac ischemic region was 3.62 ± 0.44 ID/g 30 min post injection. SPECT imaging showed a prominent uptake of 99mTc-nanoconjugate in EPO-BcR expressing ischemic heart. © 202

Corrigendum to �Technetium-99 m-PEGylated dendrimer-G2-(Dabcyle-Lys6,Phe7)-pHBSP: A novel Nano-Radiotracer for molecular and early detecting of cardiac ischemic region� Bioorg. Chem. 98 (2020) 103731(S0045206819321364)(10.1016/j.bioorg.2020.103731)

The authors regret �An improve the affiliation of Ahmad Bitarafan-Rajabic as stated here: cEchocardiography Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran. dCardiovascular Interventional Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.� The correct affiliations have been updated as above. The authors would like to apologise for any inconvenience caused. © 2020 Elsevier Inc

Induction of immune responses by protein vaccines formulated with adjuvants against Leishmania major in vivo

We used TSA as a principal antigen of Leishmania major with adjuvants. The aim of this research was to assess the efficacy of protein vaccine in the presence of Montanide vis-à -vis chitosan nanoparticle. The expression of recombinant protein was confirmed with SDS (sodium dodecyl sulfate) page and Western blotting. A total of 36 BALB/c mice were divided into six groups (TSA/high chitosan, TSA/low chitosan, TSA/Montanide, high chitosan, low chitosan, and PBS groups) and subcutaneously immunized with 20 mg of vaccine at three time intervals on days 0, 14, and 28. The mice were challenged with parasites 21 days after the final immunization. For assaying lymphocyte proliferation, the Brdu test and for evaluation of IgG subclasses and cytokines, the ELISA method was carried out. No statistically noteworthy variation was found between the vaccinated groups before and after the infectious challenge or intervention in terms of IgG and IFN-γ values. Statistically, significant difference was seen among the vaccinated and control groups in terms of IgG and IFN-γ. In terms of IL-4 before and after intervention, no statistically substantial difference was noted in the vaccinated and control groups, whereas, IgG isotypes rose to a great extent prior to and following intervention in all vaccine-immunized groups as compared with control groups. The formulated recombinant TSA protein vaccine with adjuvants induced lymphocytes proliferation and increased cytokines and antibodies as compared with the control groups. Given their potency, the formulated candidate vaccines may be recommended for further studies. © 2019, Springer-Verlag London Ltd., part of Springer Nature