Titel
Combination of Drug Delivery Properties of PAMAM Dendrimers and Cytotoxicity of Platinum(IV) Complexes—A More Selective Anticancer Treatment?
Autor*in
Petra Vician
Center for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna
... show all
Abstract
Based on their drug delivery properties and activity against tumors, we combined PAMAM dendrimers with various platinum(IV) complexes in order to provide an improved approach of anticancer treatment. Platinum(IV) complexes were linked to terminal NH2 moieties of PAMAM dendrimers of generation 2 (G2) and 4 (G4) via amide bonds. Conjugates were characterized by 1H and 195Pt NMR spectroscopy, ICP-MS and in representative cases by pseudo-2D diffusion-ordered NMR spectroscopy. Additionally, the reduction behavior of conjugates in comparison to corresponding platinum(IV) complexes was investigated, showing a faster reduction of conjugates. Cytotoxicity was evaluated via the MTT assay in human cell lines (A549, CH1/PA-1, SW480), revealing IC50 values in the low micromolar to high picomolar range. The synergistic combination of PAMAM dendrimers and platinum(IV) complexes resulted in up to 200 times increased cytotoxic activity of conjugates in consideration of the loaded platinum(IV) units compared to their platinum(IV) counterparts. The lowest IC50 value of 780 ± 260 pM in the CH1/PA-1 cancer cell line was detected for an oxaliplatin-based G4 PAMAM dendrimer conjugate. Finally, in vivo experiments of a cisplatin-based G4 PAMAM dendrimer conjugate were performed based on the best toxicological profile. A maximum tumor growth inhibition effect of 65.6% compared to 47.6% for cisplatin was observed as well as a trend of prolonged animal survival.
Stichwort
platinum(IV) complexesPAMAM dendrimersanticancerdrug delivery
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
phaidra.univie.ac.at/o:2007837
Erschienen in
Titel
Pharmaceutics
Band
15
Ausgabe
5
ISSN
1999-4923
Erscheinungsdatum
2023
Publication
MDPI AG
Fördergeber
Universität Wien — Uni:docs
Erscheinungsdatum
2023
Zugänglichkeit
Rechte
Rechteangabe
© 2023 by the authors
Universität Wien | Universitätsring 1 | 1010 Wien | T
+43-1-4277-0