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Cholesterol-targeted anticancer and apoptotic effects of anionic and polycationic amphiphilic cyclodextrin nanoparticles

AuthorsVaran, Gamze; Öncül, Selin; Ercan, Ayse; Benito, Juan M. ; Ortiz Mellet, Carmen; Bilensoy, Erem
Cell culture
Issue DateOct-2016
CitationJournal of Pharmaceutical Sciences 105(10): 3172-3182 (2016)
AbstractAmphiphilic cyclodextrins (CDs) are biocompatible derivatives of natural CDs and are able to form nanoparticles or polyplexes spontaneously. In this study, nanoparticles prepared from nonionic (6OCaproβCD) or cationic amphiphilic CD (PC βCDC6) were used comparatively to develop nanoparticles intended for breast cancer therapy. The characterization of these nanoparticles was performed both by in vitro and cell culture studies. Furthermore, the apoptotic and cytotoxic effects of blank amphiphilic CDs were demonstrated by various mechanistic methods including Caspase-8 activity, lipid peroxidation assay, TUNEL assay, Tali-based image analysis, cholesterol assay, and gene expression studies. Blank nanoparticles exerted cytotoxicity against a variety of cancer cells (MCF-7, HeLa, HepG2, and MB49) but none to healthy cells (L929, G/G). Interestingly, blank 6OCaproβCD and blank PC βCDC6 derivatives were found to be intrinsically effective on cell number and membrane integrity of MCF-7 cells in apoptosis studies. Further in-depth studies were performed to elucidate the selective mechanism of anticancer action in MCF-7 cells caused by these amphiphilic CDs. In conclusion, blank amphiphilic CD nanoparticles induced apoptosis through mitochondrial pathway targeted to cholesterol microdomains in cancer cell membrane.
Publisher version (URL)http://doi.org/10.1016/j.xphs.2016.06.021
Appears in Collections:(IIQ) Artículos
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