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Permanent URI for this collectionhttps://hdl.handle.net/11443/932

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Subject: search.filters.subject.Autophagy

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    Treatment of breast cancer with autophagy inhibitory microRNAs carried by AGO2-conjugated nanoparticles
    (BMC, 2020-01-01) Unal, Ozlem; Akkoc, Yunus; Kocak, Muhammed; Nalbat, Esra; Dogan-Ekici, Asiye Isin; Yagci Acar, Havva; Gozuacik, Devrim
    Nanoparticle based gene delivery systems holds great promise. Superparamagnetic iron oxide nanoparticles (SPIONs) are being heavily investigated due to good biocompatibility and added diagnostic potential, rendering such nanoparticles theranostic. Yet, commonly used cationic coatings for efficient delivery of such anionic cargos, results in significant toxicity limiting translation of the technology to the clinic. Here, we describe a highly biocompatible, small and non-cationic SPION-based theranostic nanoparticles as novel gene therapy agents. We propose for the first-time, the usage of the microRNA machinery RISC complex component Argonaute 2 (AGO2) protein as a microRNA stabilizing agent and a delivery vehicle. In this study, AGO2 protein-conjugated, anti-HER2 antibody-linked and fluorophore-tagged SPION nanoparticles were developed (SP-AH nanoparticles) and used as a carrier for an autophagy inhibitory microRNA, MIR376B. These functionalized nanoparticles selectively delivered an effective amount of the microRNA into HER2-positive breast cancer cell lines in vitro and in a xenograft nude mice model of breast cancer in vivo, and successfully blocked autophagy. Furthermore, combination of the chemotherapy agent cisplatin with MIR376B-loaded SP-AH nanoparticles increased the efficacy of the anti-cancer treatment both in vitro in cells and in vivo in the nude mice. Therefore, we propose that AGO2 protein conjugated SPIONs are a new class of theranostic nanoparticles and can be efficiently used as innovative, non-cationic, non-toxic gene therapy tools for targeted therapy of cancer.
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    Survival by self-destruction: A role for autophagy in the placenta?
    (W B SAUNDERS CO LTD, 2012-01-01) Bildirici, I.; Longtine, M. S.; Chen, B.; Nelson, D. M.
    Autophagy is a burgeoning area of research from yeast to humans. Although previously described as a death pathway, autophagy is now considered an important survival phenomenon in response to environmental stressors to which most organs are exposed. Despite an ever expanding literature in non-placental cells, studies of autophagy in the placenta are lagging. We review the regulation of autophagy, summarize available placental studies of autophagy, and highlight potential areas for future research. We believe that such studies will yield novel insights into how placentas protect the survival of the species by ``self-eating{''}. (C) 2012 Elsevier Ltd. All rights reserved.