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Publication
Biological Effects in Cancer Cells of Mono- and Bidentate Conjugation of Cisplatin on PAMAM Dendrimers: A Comparative Study
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Advisor(s)
Abstract(s)
Cisplatin (cis-diamminedichloroplatinum(II)) is a potent chemotherapeutic agent com monly used to treat cancer. However, its use also leads to serious side effects, such as nephrotoxicity,
ototoxicity, and cardiotoxicity, which limit the dose that can be safely administered to patients. To
minimize these problems, dendrimers may be used as carriers for cisplatin through the coordination
of their terminal functional groups to platinum. Here, cisplatin was conjugated to half-generation
anionic PAMAM dendrimers in mono- and bidentate forms, and their biological effects were as sessed in vitro. After preparation and characterization of the metallodendrimers, their cytotoxicity
was evaluated against several cancer cell lines (A2780, A2780cisR, MCF-7, and CACO-2 cells) and
a non-cancer cell line (BJ cells). The results showed that all the metallodendrimers were cytotoxic
and that the cytotoxicity level depended on the cell line and the type of coordination mode (mono- or
bidentate). Although, in this study, a correlation between dendrimer generation (number of carried
metallic fragments) and cytotoxicity could not be completely established, the monodentate coordina tion form of cisplatin resulted in lower IC50 values, thus revealing a more accessible cisplatin release
from the dendritic scaffold. Moreover, most of the metallodendrimers were more potent than the
cisplatin, especially for the A2780 and A2780cisR cell lines, which showed higher selectivity than for
non-cancer cells (BJ cells). The monodentate G0.5COO(Pt(NH3
)2Cl)8 and G2.5COO(Pt(NH3
)2Cl)32
metallodendrimers, as well as the bidentate G2.5COO(Pt(NH3
)2
)16 metallodendrimer, were even
more active towards the cisplatin-resistant cell line (A2780cisR cells) than the correspondent cisplatin sensitive one (A2780 cells). Finally, the effect of the metallodendrimers on the hemolysis of human
erythrocytes was neglectable, and metallodendrimers’ interaction with calf thymus DNA seemed to
be stronger than that of free cisplatin.
Description
Keywords
Cisplatin Anionic PAMAM dendrimer Monodentate Bidentate Anticancer Metallodendrimer . Faculdade de Ciências Exatas e da Engenharia Centro de Química da Madeira
Citation
: Camacho, C.; Maciel, D.; Tomás, H.; Rodrigues, J. Biological Effects in Cancer Cells of Mono- and Bidentate Conjugation of Cisplatin on PAMAM Dendrimers: A Comparative Study. Pharmaceutics 2023, 15, 689. https://doi.org/10.3390/ pharmaceutics15020689
Publisher
MDPI