Autophagy Modulators: Mechanistic Aspects and Drug Delivery Systems
by
Shima Tavakol 1,†, Milad Ashrafizadeh 2,†
, Shuo Deng 3, Maryam Azarian 4,5, Asghar Abdoli 6, Mahsa Motavaf 7, Delaram Poormoghadam 8, Hashem Khanbabaei 9, Elham Ghasemipour Afshar 10, Ali Mandegary 10, Abbas Pardakhty 10, Celestial T. Yap 3, Reza Mohammadinejad 11,* and Alan Prem Kumar 12,13,*
Shima Tavakol 1,†, Milad Ashrafizadeh 2,†, Shuo Deng 3, Maryam Azarian 4,5, Asghar Abdoli 6, Mahsa Motavaf 7, Delaram Poormoghadam 8, Hashem Khanbabaei 9, Elham Ghasemipour Afshar 10, Ali Mandegary 10, Abbas Pardakhty 10, Celestial T. Yap 3, Reza Mohammadinejad 11,* and Alan Prem Kumar 12,13,*
1
Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran P.O. Box 1449614525, Iran
2
Department of basic science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz 1455742, Iran
3
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
4
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran 1477893855, Iran
5
Departament de Bioquímica i Biologia Molecular, Institut de Biotecnologia i Biomedicina (IBB), Universitat Autónoma de Barcelona, 08193 Barcelona, Spain
6
Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran 1316943551, Iran
7
Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran 14115-111, Iran
8
Department of Medical Nanotechnology, Faculty of Advanced Sciences & Technology, Pharmaceutical Sciences Branch, Islamic Azad University, (IAUPS), Tehran P.O. Box 1916893813, Iran
9
Medical Physics Department, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 61357-15794, Iran
10
Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman P.O. Box 7616911319, Iran
11
Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman P.O. Box 1355576169, Iran
12
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117 600, Singapore
13
Cancer Science Institute of Singapore, National University of Singapore, Singapore 1192288, Singapore
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biomolecules 2019, 9(10), 530; https://doi.org/10.3390/biom9100530
Received: 18 August 2019 / Revised: 14 September 2019 / Accepted: 18 September 2019 / Published: 25 September 2019
(This article belongs to the Special Issue Antitumor Agents from Natural Sources)
Autophagy modulation is considered to be a promising programmed cell death mechanism to prevent and cure a great number of disorders and diseases. The crucial step in designing an effective therapeutic approach is to understand the correct and accurate causes of diseases and to understand whether autophagy plays a cytoprotective or cytotoxic/cytostatic role in the progression and prevention of disease. This knowledge will help scientists find approaches to manipulate tumor and pathologic cells in order to enhance cellular sensitivity to therapeutics and treat them. Although some conventional therapeutics suffer from poor solubility, bioavailability and controlled release mechanisms, it appears that novel nanoplatforms overcome these obstacles and have led to the design of a theranostic-controlled drug release system with high solubility and active targeting and stimuli-responsive potentials. In this review, we discuss autophagy modulators-related signaling pathways and some of the drug delivery strategies that have been applied to the field of therapeutic application of autophagy modulators. Moreover, we describe how therapeutics will target various steps of the autophagic machinery. Furthermore, nano drug delivery platforms for autophagy targeting and co-delivery of autophagy modulators with chemotherapeutics/siRNA, are also discussed.
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Keywords:
autophagy; mTOR; AMPK; Nanocarriers; combination therapy; cancer; siRNA
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
MDPI and ACS Style
Tavakol, S.; Ashrafizadeh, M.; Deng, S.; Azarian, M.; Abdoli, A.; Motavaf, M.; Poormoghadam, D.; Khanbabaei, H.; Ghasemipour Afshar, E.; Mandegary, A.; Pardakhty, A.; Yap, C.T.; Mohammadinejad, R.; Kumar, A.P. Autophagy Modulators: Mechanistic Aspects and Drug Delivery Systems. Biomolecules 2019, 9, 530.
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