Sommerfeld, Nadine S.;
Hejl, Michaela;
Klose, Matthias H. M.;
Schreiber‐Brynzak, Ekaterina;
Bileck, Andrea;
Meier, Samuel M.;
Gerner, Christopher;
Jakupec, Michael A.;
Galanski, Mathea Sophia;
Keppler, Bernhard K.
Low‐Generation Polyamidoamine Dendrimers as Drug Carriers for Platinum(IV) Complexes
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Medientyp:
E-Artikel
Titel:
Low‐Generation Polyamidoamine Dendrimers as Drug Carriers for Platinum(IV) Complexes
Beteiligte:
Sommerfeld, Nadine S.;
Hejl, Michaela;
Klose, Matthias H. M.;
Schreiber‐Brynzak, Ekaterina;
Bileck, Andrea;
Meier, Samuel M.;
Gerner, Christopher;
Jakupec, Michael A.;
Galanski, Mathea Sophia;
Keppler, Bernhard K.
Erschienen:
Wiley, 2017
Erschienen in:European Journal of Inorganic Chemistry
Sprache:
Englisch
DOI:
10.1002/ejic.201601205
ISSN:
1434-1948;
1099-0682
Entstehung:
Anmerkungen:
Beschreibung:
<jats:p>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<jats:sub>50</jats:sub> 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.</jats:p>