Low-Generation Polyamidoamine Dendrimers as Drug Carriers for Platinum(IV) Complexes
- Author(s)
- Nadine S. Sommerfeld, Michaela Hejl, Matthias H. M. Klose, Ekaterina Schreiber-Brynzak, Andrea Bileck, Samuel M. Meier, Christopher Gerner, Michael A. Jakupec, Mathea Sophia Galanski, Bernhard K. Keppler
- Abstract
An unsymmetrically carboxylated platinum(IV) analogue of oxaliplatin was coupled to low-generation polyamidoamine dendrimers (PAMAM) with amino-terminated surfaces [generations two (G-2) and four (G-4)]. 1D and 2D diffusion NMR spectroscopy and high-resolution HPLC–MS/MS were used to characterise the platinum complexes and drug–dendrimer conjugates. The average loads of platinum(IV) complex per dendrimer were determined by inductively coupled plasma MS (ICP-MS), and maximum loads of 38 % (six platinum units per dendrimer molecule) for the smaller G-2 and 34 % (22 platinum units per dendrimer molecule) for G-4 were obtained. As a result of this loading, the average diameters increased from 26 to 34 Å (30 %, G-2) and from 46 to 63 Å (38 %, G-4). The in vitro cytotoxicities of the free platinum(IV) complex, the complex-loaded dendrimers and the free PAMAM analogues G-2 and G-4 were evaluated in the cisplatin-sensitive ovarian cell line CH1/PA1 as well as in rather cisplatin-insensitive colon (SW480) and lung (A549) carcinoma cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Although the free platinum(IV) compound displayed a rather moderate activity, the drug–dendrimer complexes showed load- and size-dependent behaviour with IC
50 values down to the low-nanomolar range. In the cisplatin-insensitive cell lines, the benefit of this platinum load primarily consists of added cytostatic rather than cytocidal effects, on the basis of the results from annexin V/PI (PI = propidium iodide) assays for apoptosis/necrosis induction.
- Organisation(s)
- Department of Inorganic Chemistry, Department of Analytical Chemistry, NMR Centre
- Journal
- European Journal of Inorganic Chemistry
- Volume
- 2017
- Pages
- 1713-1720
- No. of pages
- 8
- ISSN
- 1434-1948
- DOI
- https://doi.org/10.1002/ejic.201601205
- Publication date
- 03-2017
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 301206 Pharmacology
- Keywords
- ASJC Scopus subject areas
- Inorganic Chemistry
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/07d202e6-af98-472f-b11f-7f80643e4e64