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      An understanding of mitochondria and its role in targeting nanocarriers for diagnosis and treatment of cancer

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          Abstract

          Nanotechnology has changed the entire paradigm of drug targeting and has shown tremendous potential in the area of cancer therapy due to its specificity. In cancer, several targets have been explored which could be utilized for the better treatment of disease. Mitochondria, the so-called powerhouse of cell, portrays significant role in the survival and death of cells, and has emerged as potential target for cancer therapy. Direct targeting and nanotechnology based approaches can be tailor-made to target mitochondria and thus improve the survival rate of patients suffering from cancer. With this backdrop, in present review, we have reemphasized the role of mitochondria in cancer progression and inhibition, highlighting the different targets that can be explored for targeting of disease. Moreover, we have also summarized different nanoparticulate systems that have been used for treatment of cancer via mitochondrial targeting.

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          Most cited references146

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          Understanding the Warburg effect: the metabolic requirements of cell proliferation.

          In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed "the Warburg effect." Aerobic glycolysis is an inefficient way to generate adenosine 5'-triphosphate (ATP), however, and the advantage it confers to cancer cells has been unclear. Here we propose that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. Supporting this idea are recent studies showing that (i) several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass; and that (ii) certain cancer-associated mutations enable cancer cells to acquire and metabolize nutrients in a manner conducive to proliferation rather than efficient ATP production. A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer.
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            Cancer immunotherapy comes of age.

            Activating the immune system for therapeutic benefit in cancer has long been a goal in immunology and oncology. After decades of disappointment, the tide has finally changed due to the success of recent proof-of-concept clinical trials. Most notable has been the ability of the anti-CTLA4 antibody, ipilimumab, to achieve a significant increase in survival for patients with metastatic melanoma, for which conventional therapies have failed. In the context of advances in the understanding of how tolerance, immunity and immunosuppression regulate antitumour immune responses together with the advent of targeted therapies, these successes suggest that active immunotherapy represents a path to obtain a durable and long-lasting response in cancer patients.
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              Mitochondria as sensors and regulators of calcium signalling.

              During the past two decades calcium (Ca(2+)) accumulation in energized mitochondria has emerged as a biological process of utmost physiological relevance. Mitochondrial Ca(2+) uptake was shown to control intracellular Ca(2+) signalling, cell metabolism, cell survival and other cell-type specific functions by buffering cytosolic Ca(2+) levels and regulating mitochondrial effectors. Recently, the identity of mitochondrial Ca(2+) transporters has been revealed, opening new perspectives for investigation and molecular intervention.
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                Author and article information

                Contributors
                Journal
                Asian J Pharm Sci
                Asian J Pharm Sci
                Asian Journal of Pharmaceutical Sciences
                Shenyang Pharmaceutical University
                1818-0876
                2221-285X
                10 November 2020
                July 2021
                10 November 2020
                : 16
                : 4
                : 397-418
                Affiliations
                [0001]National Institute of Pharmaceutical Education and Research (NIPER) Ahmedabad, Palaj, Opp. Air force station headqtrs, Gandhinagar 382355, India
                Author notes
                [* ]Corresponding author. mtbitat@ 123456gmail.com
                [1]

                Current affiliation: Graduate School of Pharmacy, Gujarat Technological University, Gandhinagar Campus Nr. Government Polytechnic K-6 Circle, E-4 Electronic Estate G.I.D.C, Sector - 26, Gandhinagar 382028, India.

                Article
                S1818-0876(20)30523-7
                10.1016/j.ajps.2020.10.002
                8520044
                34703491
                73dc75f4-5308-42ba-9bb9-0399f7e8c131
                © 2020 Shenyang Pharmaceutical University. Published by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 26 April 2020
                : 24 September 2020
                : 7 October 2020
                Categories
                Review

                mitochondrial targeting,cancer,nanocarriers,photodynamic therapy,photothermal therapy

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