Synthesis and Evaluation of 198Au/PAMAM-MPEG-FA against Cancer Cells
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Published:2020-08-20
Issue:10
Volume:20
Page:1250-1265
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ISSN:1871-5206
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Container-title:Anti-Cancer Agents in Medicinal Chemistry
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language:en
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Short-container-title:ACAMC
Author:
Rezaei Reza1, Darzi Simin Janitabar2ORCID, Yazdani Mahnaz3
Affiliation:
1. Department of Biochemistry, Faculty of Science, Zanjan University, 45371-38791, Zanjan, Iran 2. Nuclear Science & Technology Research Institute, Materials and Nuclear Fuel Research School, Tehran, 14395-836, Iran 3. R&D Department, Toronto Institute of Pharmaceutical Technology, Toronto, Ontario, M1P 4X4, Canada
Abstract
Background:
There is a significant dearth of clinical biochemistry researches to evaluate the facility
of exploitation of folate targeted radioactive gold-labeled anti-cancer drugs against various cancer cell lines.
Objective:
The aim of this paper was to develop a gold-based compound with an efficient therapeutic potential
against breast cancer. To this end, the synthesis of the 198Au/PAMAM-MPEG-FA composite was considered here.
Methods:
The radioactive gold (198Au) nanoparticles were encapsulated into Folic acid (FA)-targeted Polyamidoamine
dendrimer (PAMAM) modified with Maleimide-Polyethylene glycol Succinimidyl Carboxymethyl
ester (MPEG). After that, anticancer assessments of the prepared 198Au/PAMAM-MPEG-FA hybrid mater
against breast cancer were investigated.
:
Further studies were also devised to compare the anticancer capabilities of the 198Au/PAMAM-MPEG-FA composite
with the synthesized P-MPEG, 197Au/P-MPEG, 197Au/P-MPEG-FA, 197Au/P-FA and 198Au/P-MPEG-FA
conjugates. The prepared drugs were characterized by means of various analytical techniques. The radionuclidic
purity of the 198Au/P-MPEG-FA solution was determined using High Purity Germanium (HPGe) spectroscopy and
its stability in the presence of human serum was studied. The cell uptake and toxicity of the prepared drugs were
evaluated in vitro, and some comparative studies of the toxicity of the drugs were conducted towards the MCF7
(Human breast cancer cell), 4T1 (Mice breast adenocarcinoma cell) and C2C12 (Mice muscle normal cell).
Results:
The results showed that cell uptake of 198Au/P-MPEG-FA nanoparticles is high in the 4T1 cell line and
the order of uptake is as 4T1> MCF7> C2C12. Moreover, of the tested compounds, 198Au/P-MPEG-FA had the
highest toxicity towards the cancerous 4T1 and MCF7 in all concentrations after 24, 48 and 72h (P < 0.001).
Furthermore, the cytotoxicity of the drugs was concentration-dependent.
Conclusion:
On the basis of the present research, 198Au/P-MPEG-FA has been proposed as a good candidate for the
induction of cell death in breast cancer, although further experimental and clinical investigations are required.
Funder
Iran National Science Foundation Zanjan University
Publisher
Bentham Science Publishers Ltd.
Subject
Cancer Research,Pharmacology,Molecular Medicine
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