Nano-scaled Diethylene Triamine Pent Acetic Acid (N-DTPA):

Novel Anti-Wilson's Disease Cell Model ^Δ

¹Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

²Medical Physics and Biomedical Engineering and Nanomedicine Department, Faculty of Medicine, Shahid Beheshti Medical University, Tehran, Iran

³Hepatitis and AIDS Dept. Pasteur Institute of Iran, Tehran, Iran

⁴Department of Medicinal and Radiopharmaceutical Chemistry, Tehran University of Medical Sciences, Tehran, Iran

⁵Faculty of Chemistry, Laboratory of Natural Carbohydrates and Biopolymer, University of Tabriz, Tabriz, Iran

*Corresponding author:

Dr Mehdi Shafiee Ardestani

Assistant Professor

Hepatitis and AIDS Department, Pasteur Institute of Iran

Department of Medicinal and Radiopharmaceutical Chemistry, Tehran University of Medical Sciences

Tehran, Iran

Tel/Fax: +9866953311

Email: shafieeardestani@gmail.com

^Δ This paper is a thesis submitted for M. Sc. Degree in Biochemistry by Mrs. Saba Zakery.

Abstract

       Wilson's disease (WD) is an autosomal recessive disorder in which copper metabolism is impaired. In fact, copper accumulates in various organs and tissues can be seen and causes toxic effects in various tissues including liver, brain, kidneys and eyes. Sulfur amino acid is a metabolite of D-penicillamine and penicillamine and copper Chlator is a factor that causes urinary excretion of copper and WD therapeutic agent as well. The interesting thing about the neurological symptoms of Wilson's disease with penicillamine is the drug may worsen or even in an asymptomatic patient, the treatment may be creating symptoms. DTPA is a pentavalent compound containing carboxylic DTPA is a chemical compound that is used in radiation therapy and MRI. It can give the metal chelate with iron, copper and other cations can be conjugated and also treatment of internal body pollution caused by various elements, including raDOIactive elements. DTPA could not be lonely absorbed by the cell. The goal is to conjugate it with the G2 Dendrimer (Nanosized anionic linear biocompatible polymer) to bring it to the nano size and increase the intracellular uptake compared to the ground state. Based on the hypothesis, nanoconjugated DTPA-Dendrimer G2 was synthesized and then evaluated on Hep G2 WD cell model in vitro and the results showed a good effectiveness without any toxicity for the conjugate in decreasing the intracellular copper level comparing to gold standard D-penicillamine respectively. Based on the findings the nanosized conjugate seems to have very good prognoses and clinical future and this needs to be further investigated.

Keywords: Wilson's disease (WD), nanosized conjugate, DTPA, Anionic linear globular Dendrimer, HepG2.

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