期刊
JOURNAL OF NANOPARTICLE RESEARCH
卷 22, 期 1, 页码 -出版社
SPRINGER
DOI: 10.1007/s11051-019-4708-x
关键词
Metallacarborane; NTA; Nanoparticles; BSA; Drug formulation
资金
- Saxon State Ministry for Sciences and Arts (SMWK) [LAU-R-N-11-2-0615]
- German chemical industry association (VCI) [197021]
- Graduate School Leipzig School of Natural Sciences - Building with Molecules and Nano-objects (BuildMoNa)
- European Regional Development Fund (ERDF, Europaischer Fond fur Regionale Entwicklung EFRE, Europe funds Saxony) [100195374]
We report on the unique self-assembling properties of one molybdacarborane (1) and two ruthenacarborane complexes (2 and 3) to spontaneously form nanoparticles alone or in combination with bovine serum albumin (BSA) in a 10:1 molar ratio (BSA:metallacarborane). The maverick behaviour of the metallacarboranes in aqueous media was investigated using several spectroscopic techniques, including nanoparticle tracking analysis, UV-Vis, fluorescence, Rayleigh light scattering and NMR spectroscopy, as well as MALDI-TOF mass spectrometry, from which a molecular picture of the nanoparticles was developed. The metallacarborane-albumin nanoparticles showed optimal stability in phosphate buffer (pH 7.4), retaining a mostly monomodal dispersion over 24 h, in contrast to the highly polydispersed nanoparticles of 1-3 alone. The three metallacarboranes were tested in vitro against the MCF-7 (breast carcinoma) cell line, using a BSA-free and a BSA-containing formulation. Surprisingly, the latter induced a significant increase in the cytotoxicity of 1, whereby it did not greatly affect the activity profile of 2 and 3. Finally, label-free confocal Raman imaging was applied to visualise the uptake of the metallacarboranes into single cells. The size of intracellular aggregates in the cytoplasm ranged from 300 nm to 5 mu m. The discussed formulation concept is proposed as a new method to increase the bioactivity and the biological stability of poorly water-soluble (metalla)carboranes.
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