title: Cholesterol-Targeted Anticancer and Apoptotic Effects of Anionic and Polycationic Amphiphilic Cyclodextrin Nanoparticles.
abstract: Amphiphilic 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.
authors.affiliation: Department of Nanotechnology and Nanomedicine, Hacettepe University, Ankara, Turkey.
authors.forename: Gamze
authors.initials: G
authors.lastname: Varan
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
authors.forename: Selin
authors.initials: S
authors.lastname: Öncül
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
authors.forename: Ayşe
authors.initials: A
authors.lastname: Ercan
authors.affiliation: Institute for Chemical Research, CSIC-University of Sevilla, Sevilla, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Benito
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, University of Sevilla, Sevilla, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ortiz Mellet
authors.affiliation: Department of Nanotechnology and Nanomedicine, Hacettepe University, Ankara, Turkey; Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey. Electronic address: eremino@hacettepe.edu.tr.
authors.forename: Erem
authors.initials: E
authors.lastname: Bilensoy
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002784:Cholesterol / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000378:metabolism; D011073:Polyamines / Q000008:administration & dosage* / Q000378:metabolism; D000071228:Polyelectrolytes; D013501:Surface-Active Agents / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002784:Cholesterol; D011073:Polyamines; D000071228:Polyelectrolytes; D013501:Surface-Active Agents
keywords: apoptosis; cancer; cell culture; cyclodextrin; nanoparticles