Mn2+ - Negatively Charged Pegylated Dendrimer G2-Tryptophan: Novel Nano Magnetic Resonance Imaging Agent
Advances in Applied Physiology
Volume 2, Issue 1, October 2017, Pages: 1-9
Received: Dec. 24, 2016; Accepted: Mar. 22, 2017; Published: Jul. 14, 2017
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Asma Keshavarz, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
Soodeh Hajbabaei, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
Jafar Sojoodi, Pharma Chemie Company, Tehran, Iran
Mostafa Saffari, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
Mohammad Amin Aghaii Afshar, Department of Medical Nanotechnology, Faculty of Advanced Sciences &Technology, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran
Fatemeh Monnavari, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
Esmaeil Mohammadi Pargoo, Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
Rahimeh Rasouli, Medical Nanotechnologies in Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
Hadi Hejazinia, Department of Radio Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Artin Assadi, Department of Radio Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Leila Badrzadeh, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
Shirin Abbasnezhad, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
Seyed Ataollah Sadat Shandiz, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
Mohammad Saffari, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Masood Bamedi, Depertment of Periodontology and Oral and Dental Disease Research Center, Zahedan University of Medical Science, Zahedan, Iran
Mehdi Shafiee Ardestani, Department of Radio Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
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Due to the new proclamation of the harmful symptoms of Gd (III) based MRI differentiate operators in the patients with harmed renal capacities, there is a solid consideration on emerging substitute differentiate specialists for MRI. A polymer with core of PEG and citrus extract as a shell was created for double modular imaging. After amalgamation of the polymer, ALGD-Trp Conjugate and after that Mn2+ stacked on the dendrimer. Differentiate upgraded MRI of the focused on double imaging operator was assessed by AFM magnifying lens. Growth is one of driving reason for death in everywhere throughout the world. Early determination of tumor known as a decent solution. Achieving a capable and non-obtrusive contrast agent with high specificity, sensitivity and capacity to target cancer cells are essential. Among of different malignancies distinguishing strategies, Magnetic Resonance Imaging is an important technique, however its burdens including low resolution, In this study, Tryptophan was appended on the Anionic direct globular dendrimer with polyethylene glycol center and citrus extract bunches around it. Tryptophan was utilized to enhance intra-cell take-up and gathering in human bosom malignancy cells lastly differentiate operator (Mn2+) stacked in orchestrated dendrimers. The contrast agent was characterized with different techniques such as FT-IR, FTIR, Zeta sizer, UV-spectroscopy. ICP-AES was used to assess the intra-cell take-up of Mn2+ iones. Cytotoxicity studies and evaluation of cell passing mechanism were performed in bosom tumor MCF-7 cell line. Then, impact of various grouping of new difference specialist on T1 and T2 assessed in-vitro utilizing MR imaging. In light of the outcomes exhibited that Mn2+ - Anionic straight globular dendrimer G2-Tryptophancontrastagentdid not demonstrate any significant toxicity (cancer and ordinary cells), The outcomes demonstrated the new focused on nano differentiate specialist fitting accumulation in the tumor cells and solid T1intense flag on compared to Magnevist as a standard CA. This novel complexity specialist can be presented as a decent CA applicant in early identification of tumor.
Synthesis, Biological Activity, Mn2+ Dendrimer G2-Tryptophan, MRI
To cite this article
Asma Keshavarz, Soodeh Hajbabaei, Jafar Sojoodi, Mostafa Saffari, Mohammad Amin Aghaii Afshar, Fatemeh Monnavari, Esmaeil Mohammadi Pargoo, Rahimeh Rasouli, Hadi Hejazinia, Artin Assadi, Leila Badrzadeh, Shirin Abbasnezhad, Seyed Ataollah Sadat Shandiz, Mohammad Saffari, Masood Bamedi, Mehdi Shafiee Ardestani, Mn2+ - Negatively Charged Pegylated Dendrimer G2-Tryptophan: Novel Nano Magnetic Resonance Imaging Agent, Advances in Applied Physiology. Vol. 2, No. 1, 2017, pp. 1-9. doi: 10.11648/j.aap.20170201.11
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Mousavi SM, Gouya MM, Ramazani R, Davanlou M, Hajsadeghi N, Seddighi Z. Cancer incidence and mortality in Iran. Annals of Oncology 2009, 20:556-563.
Denecke T, Rau B, Hoffmann K-T, Hildebrandt B, Ruf J, Gutberlet M, et al. Comparison of CT, MRI and FDG-PET in response prediction of patients with locally advanced rectal cancer after multimodal preoperative therapy: is there a benefit in using functional imaging? European radiology 2005, 15:1658-1666.
Kalita J, Misra U. Comparison of CT scan and MRI findings in the diagnosis of Japanese encephalitis. Journal of the neurological sciences 2000, 174:3-8.
Theodore WH, Dorwart R, Holmes M, Porter RJ, DiChiro G. Neuroimaging in refractory partial seizures Comparison of PET, CT, and MRI. Neurology 1986, 36:750-750.
Coughlin SS, Ekwueme DU. Breast cancer as a global health concern. Cancer epidemiology 2009, 33:315-318.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA: a cancer journal for clinicians 2015, 65:5-29.
von Schulthess GK, Steinert HC, Hany TF. Integrated PET/CT: current applications and future directions 1. Radiology 2006, 238:405-422.
Catana C, Wu Y, Judenhofer MS, Qi J, Pichler BJ, Cherry SR. Simultaneous acquisition of multislice PET and MR images: initial results with a MR-compatible PET scanner. Journal of Nuclear Medicine 2006, 7:1968-1976.
Weber WA, Grosu AL, Czernin J. Technology Insight: advances in molecular imaging and an appraisal of PET/CT scanning. Nature Clinical Practice Oncology 2008, 5:160-170.
Cassileth BR, Deng G. Complementary and alternative therapies for cancer. The oncologist 2004, 9:80-89.
Cummings B, Keane T, O'sullivan B, Wong C, Catton C. Epidermoid anal cancer: treatment by radiation alone or by radiation and 5-fluorouracil with and without mitomycin C. International Journal of Radiation Oncology* Biology* Physics 1991, 21:1115-1125.
Kuhl CK, Schrading S, Bieling HB, Wardelmann E, Leutner CC, Koenig R, et al. MRI for diagnosis of pure ductal carcinoma in situ: a prospective observational study. The Lancet 2007, 370:485-492.
Grobner T. Gadolinium–a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrology Dialysis Transplantation 2006, 21:1104-1108.
Caravan P. Strategies for increasing the sensitivity of gadolinium based MRI contrast agents. Chemical Society Reviews 2006, 5:512-523.
Aime S, Cabella C, Colombatto S, Geninatti Crich S, Gianolio E, Maggioni F. Insights into the use of paramagnetic Gd (III) complexes in MR‐molecular imaging investigations. Journal of magnetic resonance imaging 2002, 16:394-406.
Alavidjeh MS, Haririan I, Khorramizadeh MR, Ghane ZZ, Ardestani MS, Namazi H. Anionic linear-globular dendrimers: biocompatible hybrid materials with potential uses in nanomedicine. Journal of Materials Science: Materials in Medicine 2010, 21:1121-1133.
Gillies ER, Frechet JM. Dendrimers and dendritic polymers in drug delivery. Drug discovery today 2005, 10:35-43.
Patri AK, Kukowska-Latallo JF, Baker JR. Targeted drug delivery with dendrimers: comparison of the release kinetics of covalently conjugated drug and non-covalent drug inclusion complex. Advanced drug delivery reviews 2005, 57:2203-2214.
Mehdi M. Novel nanosized Gd3+-ALGD-G2-C595: in vivo dual selective MUC-1 positive tumor molecular MR imaging and therapeutic agent. Journal of Nanomedicine & Nanotechnology 2012.
Haririan I, Alavidjeh MS, Khorramizadeh MR, Ardestani MS, Ghane ZZ, Namazi H. Anionic linear-globular dendrimer-cis-platinum (II) conjugates promote cytotoxicity in vitro against different cancer cell lines. International journal of nanomedicine 2010, 5:63.
Mirzaei M, Mohagheghi M, Shahbazi-Gahrouei D, Khatami A. Novel Nanosized Gd3+-ALGD-G2-C595. In: vivo; 2012.
Khosroshahi A, Amanlou M, Sabzevari O, Daha F, Aghasadeghi M, Ghorbani M, et al. A comparative study of two novel nanosized radiolabeled analogues of methionine for SPECT tumor imaging. Current medicinal chemistry 2013, 20:123-133.
Medina SH, El-Sayed ME. Dendrimers as carriers for delivery of chemotherapeutic agents. Chemical reviews 2009, 109:3141-3157.
D'Emanuele A, Attwood D. Dendrimer–drug interactions. Advanced drug delivery reviews 2005, 57:2147-2162.
Artemov D. Molecular magnetic resonance imaging with targeted contrast agents. Journal of cellular biochemistry 2003, 90:518-524.
Christensen HN. Role of amino acid transport and countertransport in nutrition and metabolism. Physiol Rev 1990, 70:43-77.
Del Amo EM, Urtti A, Yliperttula M. Pharmacokinetic role of L-type amino acid transporters LAT1 and LAT2. European Journal of Pharmaceutical Sciences 2008, 35:161-174.
Hyde R, Taylor P, Hundal H. Amino acid transporters: roles in amino acid sensing and signalling in animal cells. Biochem. J 2003, 373:1-18.
Yoon JH, Kim YB, Kim MS, Park JC, Kook JK, Jung HM, et al. Expression and functional characterization of the system L amino acid transporter in KB human oral epidermoid carcinoma cells. Cancer letters 2004, 205:215-226.
Kobayashi H, Ishii Y, Takayama T. Expression of L‐type amino acid transporter 1 (LAT1) in esophageal carcinoma. Journal of surgical oncology 2005, 90:233-238.
Lin J, Raoof DA, Thomas DG, Greenson JK, Giordano TJ, Robinson GS, et al. L-type amino acid transporter-1 overexpression and melphalan sensitivity in Barrett's adenocarcinoma. Neoplasia 2004, 6:74-84.
Nawashiro H, Otani N, Shinomiya N, Fukui S, Ooigawa H, Shima K, et al. L‐type amino acid transporter 1 as a potential molecular target in human astrocytic tumors. International journal of cancer 2006, 119:484-492.
Nawashiro H, Otani N, Shinomiya N, Fukui S, Nomura N, Yano A, et al. The role of CD98 in astrocytic neoplasms. Human cell 2002, 15:25-31.
Nakanishi K, Matsuo H, Kanai Y, Endou H, Hiroi S, Tominaga S, et al. LAT1 expression in normal lung and in atypical adenomatous hyperplasia and adenocarcinoma of the lung. Virchows Archiv 2006, 448:142-150.
Yoon JH, Kim IJ, Kim H, Kim H-J, Jeong MJ, Ahn SG, et al. Amino acid transport system L is differently expressed in human normal oral keratinocytes and human oral cancer cells. Cancer letters 2005, 222:237-245.
KIM S-G, KIM H-H, KIM H-K, KIM C-H, CHUN HS, KANAI Y, et al. Differential expression and functional characterization of system L amino acid transporters in human normal osteoblast cells and osteogenic sarcoma cells. Anticancer research 2006, 26:1989-1996.
Shennan DB, Thomson J, Barber M, Travers M. Functional and molecular characteristics of system L in human breast cancer cells. Biochimica et Biophysica Acta (BBA)-Biomembranes 2003, 1611:81-90.
Travers M, Gow IF, Barber M, Thomson J, Shennan DB. Indoleamine 2, 3-dioxygenase activity and L-tryptophan transport in human breast cancer cells. Biochimica et Biophysica Acta (BBA)-Biomembranes 2004, 1661:106-112.
Shennan DB, Thomson J, Gow IF, Travers M, Barber M. L-leucine transport in human breast cancer cells (MCF-7 and MDA-MB-231): kinetics, regulation by estrogen and molecular identity of the transporter. Biochimica et Biophysica Acta (BBA)-Biomembranes 2004, 1664:206-216.
Shennan DB, Thomson J. Inhibition of system L (LAT1/CD98hc) reduces the growth of cultured human breast cancer cells. Oncology reports 2008, 20:885-889.
Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science 2011, 331:1565-1570.
Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nature Reviews Cancer 2012, 12:252-264.
Alimova A, Katz A, Sriramoju V, Budansky Y, Bykov AA, Zeylikovich R, et al. Hybrid phosphorescence and fluorescence native spectroscopy for breast cancer detection. Journal of biomedical optics 2007, 12:014004-014004-014006.
Betsunoh H, Fukuda T, Anzai N, Nishihara D, Mizuno T, Yuki H, et al. Increased expression of system large amino acid transporter (LAT)-1 mRNA is associated with invasive potential and unfavorable prognosis of human clear cell renal cell carcinoma. BMC cancer 2013, 13:509.
Zhang L, Pu Y, Xue J, Pratavieira S, Xu B, Achilefu S, et al. Tryptophan as the fingerprint for distinguishing aggressiveness among breast cancer cell lines using native fluorescence spectroscopy. Journal of biomedical optics 2014, 19:037005-037005.
Sartori C, Finch DS, Ralph B, Gilding K. Determination of the cation content of alginate thin films by FTi. r. spectroscopy. Polymer 1997, 38:43-51.
Vermes I, Haanen C, Steffens-Nakken H, Reutellingsperger C. A novel assay for apoptosis flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled annexin V. Journal of immunological methods 1995, 184:39-51.
Coenen HH, Kling P, Stöcklin G. Cerebral metabolism of L-[2-18F] fluorotyrosine, a new PET tracer of protein synthesis. Journal of nuclear medicine: official publication, Society of Nuclear Medicine 1989, 30:1367-1372.
Inoue T, Shibasaki T, Oriuchi N, Aoyagi K, Tomiyoshi K, Amano S, et al. ^ 1^ 8F -Methyl Tyrosine PET Studies in Patients with Brain Tumors. Journal of Nuclear Medicine 1999, 40:399-405.
Juhász C, Nahleh Z, Zitron I, Chugani DC, Janabi MZ, Bandyopadhyay S, et al. Tryptophan metabolism in breast cancers: molecular imaging and immunohistochemistry studies. Nuclear medicine and biology 2012, 39:926-932.
Mehravi B, Ardestani MS, Damercheli M, Soltanghoraee H, Ghanaldarlaki N, Alizadeh AM, et al. Breast Cancer Cells Imaging By Targeting Methionine Transporters with Gadolinium-Based Nanoprobe. Molecular Imaging and Biology 2014, 16:519-528.
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