Synthesis and Evaluation of 198Au/PAMAM-MPEG-FA against Cancer Cells

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Author(s): Reza Rezaei, Simin J. Darzi*, Mahnaz Yazdani.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

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Background: There is a significant dearth of clinical biochemistry researches to evaluate 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 the 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 drugs toxicity were conducted towards the MCF7 (Human breast cancer cell), 4T1 (Mice breast adenocarcinoma cell) and C2C12 (Mice muscle normal cell).

Results: The result showed that cell uptake of 198Au/P-MPEG-FA nanoparticles is much more in 4T1cell 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 4T1and 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 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.

Keywords: Radioactive gold, PAMAM dendrimer, Drug targeting, Cellular uptake, Toxicity, Folate

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(E-pub Ahead of Print)
DOI: 10.2174/1871520620666200220113452
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