para-Sulfonatocalix[4]arene and polyamidoamine dendrimer nanocomplexes as delivery vehicles for a novel platinum anticancer agent.

Autor: Pang CT; Faculty of Pharmacy, The University of Sydney, NSW 2006, Australia., Ammit AJ; Woolcock Emphysema Centre, Woolcock Institute of Medical Research, The University of Sydney, NSW 2037, Australia; School of Life Sciences, Faculty of Science, University of Technology, Sydney, NSW 2007, Australia., Ong YQE; Faculty of Pharmacy, The University of Sydney, NSW 2006, Australia., Wheate NJ; Faculty of Pharmacy, The University of Sydney, NSW 2006, Australia. Electronic address: nial.wheate@sydney.edu.au.
Jazyk: angličtina
Zdroj: Journal of inorganic biochemistry [J Inorg Biochem] 2017 Nov; Vol. 176, pp. 1-7. Date of Electronic Publication: 2017 Aug 08.
DOI: 10.1016/j.jinorgbio.2017.08.002
Abstrakt: Novel para-sulfonatocalix[4]arene (sCX[4]) and polyamidoamine (PAMAM) dendrimer nanocomplexes were evaluated as delivery vehicles for the platinum anticancer agent [(1,10-phenanthroline)(1S,2S-diaminocyclohexane)platinum(II)] chloride (PHENSS). Different ratios of sCX[4] to PHENSS were tested for their compatibility, with a ratio of 6:1 sCX[4]:PHENSS having the best solubility. The loading of sCX[4], and sCX[4]-bound PHENSS, onto three different generations of PAMAM dendrimers (G3.0-5.0) was examined using UV-visible spectrophotometry. The quantity of sCX[4] bound was found to increase exponentially with dendrimer size: G3, 15 sCX[4] molecules per dendrimer; G4, 37; and G5, 78. Similarly, the loading of sCX[4]-bound PHENSS also increased with increasing dendrimer size: G3, 7 PHENSS molecules per dendrimer; G4, 14; and G5, 28.5. The loading of sCX[4]-bound PHENSS molecules is significantly lower when compared with that of sCX[4], which indicates that less than half of the binding sites were occupied (45, 44, and 44%, respectively). By 1 H NMR and UV-vis analysis, the nanocomplex was found to be stable in NaCl solutions at concentrations up to 150mM. While PHENSS is more active in vitro than cisplatin against the human breast cancer cell line, MCF-7, delivery of PHENSS using the sCX[4]-dendrimer nanocomplexes, regardless of dendrimer generation, had little effect on PHENSS cytotoxicity. The results of this study may have application in the delivery of a variety of small molecule metal-based drugs for which chemical conjugation to a nanoparticle is undesired or not feasible.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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