AGRO 100 Apt-Chitosan labeled with BODIPY-FL as a novel cancer diagnostic Agent

Targeted Nano-based imaging methods have been used to precisely diagnose different diseases lately. In this research, chitosan was synthesized and confirmed using Zeta Sizer and AFM. AGRO 100 Aptamer was conjugated on the surface of chitosan nanoparticles and then conjugate labeled with BODIPY-FL. Then, in vitro assays such as XTT and uptake assessment were preformed. Data showed successful synthesis of nanoparticle and conjugate. Cellular uptake in cancer cells was increased and no significant (p value<0.05) cytotoxicity has been found on normal cells. Taking everything into account, the mentioned fluorescent labeled bioconjugate seems to be an appropriate fluorescent diagnostic agent for the future in vivo studies. Introduction: Recently, many aptamers such as MUC1, A30, AGRO 100,and etc. have been found which work as therapeutic/diagnostic agents through shape complementary with their specific cancerous cell membrane overexpressed receptors. AGRO 100 is now in the second phase of clinical trials of two cancers as a therapeutic agent and it specifically targets nucleolin which is overexpressed on the cancer cells’ surface and constrains tumor growth. Nowadays, aptamer based drug delivery/ imaging is being used as a novel pharmaceutical approach in vitro/ in vivo. These aptamers based on their ability to detect cell surface disease specific biomarkers and treat diseases are termed as smart devices in Nano-Theranostics applications. Methods and Results: In the current project, chitosan was synthesized and confirmed using Zeta Sizer (size, charge and molecular weight) and AFM. Aptamer AGRO 100 (APT AS1411 ) was conjugated successfully on the surface of chitosan nanoparticles using a covalent bond (carboxyl active groups to amine active groups) using NHS and EDC, then conjugate labeled with BODIPY-FL. Conclusion: Using AGRO 100 aptamer, chitosan nanoparticles and BODIPY-FL the desired targeted fluorescent diagnostic agent was constructed. Based on the in vitro results, no significant cytotoxicity on HEK-293 has been found. Moreover, bioconjugate had a good cellular uptake on T47D cells. Taking everything into account, the mentioned fluorescent labeled bioconjugate seems to be an appropriate fluorescent diagnostic agent for the future in vivo studies

COX inhibition: Catalepsy and Striatum Dopaminergic-GABAergic-Glutamatergic Neurotransmission

Selective COX-2 and COX-1 inhibitors were administered (i.p. acutely) to normal and parkinsonian rats, followed by the analysis of the striatal dopamine, GABA and glutamate concentrations using the microdialysis technique, simultaneously, the catalepsy of animals was evaluated. Selective COX-2 inhibition showed improving effects on the catalepsy followed by decreasing the striatum glutamatergic-GABAergic and enhancing the dopaminergic neurotransmission. Nonetheless COX inhibition had no significant improving effects on damaged Substantia Nigra Pars Compacta (SNc) neurons

Synthesis of Novel (Technetium-99m)-(DOTA-NHS-ester)-Methionine Radio Drug as a SPECT-CT Imaging Candidate

Cancer is a disease in which a group of cells show an uncontrolled growth (Cell division beyond the normal range), invasion (Penetration into and destruction of adjacent tissues), and in some cases, metastasis (Spreading to other parts of the body via lymph or blood systems). These three destructive nature of cancerous tumors distinguish them from benign tumors. Undoubtedly, early detection of cancer is associated with an increased survival of these patients. Introduction              SPECT/CT (Single Photon Emission Computed Tomography) give us a signal for cancer diagnosis. The use of radiopharmaceuticals such as technetium improves images. Technetium is one of the famous contrast agent used in this technique, which is toxic and should be used as a complex with a ligand. In this study (Technetium-99m)-(DOTA-NHS-ester)-Methionine radio drug was synthesized. Technetium-99m is an isomer of isotope-99mTC, which is attempted by isomeric transition. Methionine is an essential amino acid which has important roles in cancerous cells. DOTA was used to conjugate with Methionine and then labeled with 99mTc to improve tumor selectivity. This synthesized radio drug would be able to nominate as a SPECT-CT imaging candidate. Methods and results In this current study, a novel structure of DOTA-NHS ester conjugated to essential amino acid methionine was synthesized, and then labeled by a radionuclide technetium. The final radiopharmaceutical characterized and then studied as a contrast agent in SPECT/CT   imaging. Conclusion (Technetium-99m)-(DOTA-NHS-ester)-Methionine synthesized radio drug showed significant (P<0.05) Cellular uptake in cancerous cells in comparison with other normal cells and Cellular toxicity was observed in those cancerous cell lines. According to the final data, the synthesized radiopharmaceutical, was detected in the tumor with high and significant appearance in SPECT/CT technique

Steroidal anti inflammatory drug betamethasone significantly alters level of striatal dopamine in a rat model of Parkinson’s disease

Many scientific efforts have been well done to investigate the effects of anti inflammatory agents on the degenerative brain diseases such as Parkinson’s (PD) or Alzheimer’s disease and their affiliated sings. Previously we showed the effectiveness of steroids on rigidity of PD and in the study for further mechanistic investigation of that observation the microdialysis technique was employed to determine the striatal dopamine changes in parkinsonian rats after administration of betamethasone (0.12, 0.24 mg/kg) respectively. Our findings showed us the significant increase in the striatal dopaminergic neurotransmission (P<0.05) after administration of betamethasone comparing to the controls. These observations suggest a new mechanism for betamethasone on striatum dopaminergic neurotransmission leading us to gather further evidence about effectiveness of betamethasone in PD

Pressure responsive nanogel base on Alginate‐Cyclodextrin with enhanced apoptosis mechanism for colon cancer delivery

5‐Fluorouracil (5‐Fu) commonly use in the treatment of different kinds of cancer, but limited cellular uptake and death is still a problem. Herein, we report a simple process for the synthesis of pressure‐sensitive nanogels that indicate to be appropriate in the delivery of 5‐Fu. The hydrogels (Al‐CD) prepare by crosslinking of alginate (Al) with modified beta Cyclodextrin (β‐CD) as Crosslinker. Next, nanoparticles obtaine by an emulsification method. 5‐Fu as model drug loades into the Al‐CD nanogels easily by mixing it in aqueous solution with the nanoparticles. The results revealed that the Al‐CD nanogels are cytocompatible. They have also a noticeable drug encapsulation (82.1 ±5.7%) while they can release (in vitro controlled) 5‐Fu in conditions that imitate the intravascular pressure conditions. These nanogels can rapidly be taken up by HT‐29 cells (a colon cell line). In addition, a higher 5‐Fu intracellular accumulation and a significant cell death extension by apoptosis mechanism is notice when compare with free 5‐Fu. Accordingly, the developed nanogels can be employe as an excellent candidate to overcome the inefficiency of 5‐Fu in anticancer treatments and possibly can employe for further evaluation as a chemotherapical agent in applications beyond cancer. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 349–359, 2018.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143710/1/jbma36242.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143710/2/jbma36242_am.pd

Inhibitory effect of gold nanoparticles conjugated with interferon gamma and methionine on breast cancer cell line

AbstractObjectiveTo develop a gold nanoparticles complex conjugated with interferon-gamma (IFN-γ) and methionine along with application of hyperthermia using near-infrared laser beams for the treatment of cancer cells.MethodsGold nanorods (10 nm) were conjugated with IFN-γ and methionine using carbodiimide family and characterized after purification by dialysis bags. Breast cancer cells were cultured and incubated with gold nanorods at different concentrations followed by irradiation with near-infrared laser beam. Samples were then evaluated for their viability in order to determine the effect of treatment and variables by MTT assy.ResultsZetasizer results confirmed the conjugation of gold nanorods with methionine and IFN-γ. The median percentage of cell viability in 0.30 μg/mL concentration of gold nanorods was 82%. The cell viability reached to 85% at the same concentration of gold nanorods, which existed in the assayed complex. The results of MTT assay showed that the 0.60 μg/mL concentration of gold nanoparticles complex was toxic on tumor cells (P < 0.05). After exposure to hyperthermia, the viability of cells at 6 min decreased to 77% in 0.30 μg/mL concentration of gold nanorods complex.ConclusionsThe size and concentration of gold nanorods was not cytotoxic. However, their presence during irradiation near-infrared laser increased the number of dead cells during the treatment of cells

Mesoporous silica nanoparticles functionalized with folic acid/methionine for active targeted delivery of docetaxel

Abstract: Mesoporous silica nanoparticles (MSNs) are known as carriers with high loading capacity and large functionalizable surface area for target-directed delivery. In this study, a series of docetaxel-loaded folic acid- or methionine-functionalized mesoporous silica nanoparticles (DTX/MSN-FA or DTX/MSN-Met) with large pores and amine groups at inner pore surface properties were prepared. The results showed that the MSNs were successfully synthesized, having good pay load and pH-sensitive drug release kinetics. The cellular investigation on MCF-7 cells showed better performance of cytotoxicity and cell apoptosis and an increase in cellular uptake of targeted nanoparticles. In vivo fluorescent imaging on healthy BALB/c mice proved that bare MSN-NH2 are mostly accumulated in the liver but MSN-FA or MSN-Met are more concentrated in the kidney. Importantly, ex vivo fluorescent images of tumor-induced BALB/c mice organs revealed the ability of MSN-FA to reach the tumor tissues. In conclusion, DTX/MSNs exhibited a good anticancer activity and enhanced the possibility of targeted drug delivery for breast cancer

Treatment of oral squamous cell carcinoma using anti-HER2 immunonanoshells

Reza Fekrazad2, Neda Hakimiha3, Enice Farokhi3, Mohammad Javad Rasaee4, Mehdi Shafiee Ardestani5, Katayoun AM Kalhori2, Farzaneh Sheikholeslami1 1Research &amp;amp; Development Department, Production and Research Division of the Pasteur Institute of Iran, Karaj, Iran; 2Dental Department, AJA University of Medical Sciences, Laser Research Center, Dental Faculty, Tehran University of Medical Sciences; 3Dentistry Department, Faculty of Dentistry, Shahed University, Tehran, Iran; 4Department of Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; 5Hepatitis and AIDS Department, Pasteur Institute of Iran, Tehran Background: Worldwide, oral squamous cell carcinoma (potentially mediated by HER2) is recognized as the most commonly occurring malignant neoplasm of the oral cavity. Anti-HER2 nanobodies conjugated to gold-silica nanoshells and used as photothermal treatment for oral squamous cell carcinoma may provide a novel therapeutic alternative to current treatment for this disease. Methods: KB epithelial or HeLaS3 cell cultures (controls) were exposed to these immunonanoshells, and plasmon resonance electron initiation specific to gold was employed to burn the tumor cells. Results: Following this treatment, significant cell death occurred in the KB tumor cell cultures while there was no evidence of cellular damage or death in the HeLaS3 cell cultures. Conclusion: These findings suggest that photothermal treatment of oral squamous cell carcinoma has considerable advantages. Keywords: anti-HER2 immunonanoshells, gold-silica nanoshells, photothermal treatment, oral squamous cell carcinom