Mitochondrial targeted strategies and their application for cancer and other diseases treatment
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REVIEW
Mitochondrial targeted strategies and their application for cancer and other diseases treatment Qiuyi Li1 · Yuan Huang1 Received: 11 February 2020 / Accepted: 1 April 2020 © The Korean Society of Pharmaceutical Sciences and Technology 2020
Abstract Background Known as the main site of ATP production and intrinsic apoptosis regulator, mitochondria play vital roles in physiological functions and pathological progression. Evidences have shown that mitochondrial dysfunction correlated with a variety of diseases, especially with cancer. Mitochondria are emerged as an attractive target for diseases treatment. Area covered This review introduces efficient mitochondrial targeting strategies, and summarizes application of multiple drug delivery systems targeted to mitochondria for antitumor treatment, including anti-drug resistance, anti-metastasis and immunotherapy. Furthermore, we discuss the application and perspectives of mitochondrial targeting in treatment of other mitochondrial-related diseases. Expert opinion A number of chemotherapeutics exert their efficacy in specific sub-organelles. Targeting drugs to one certain organelle would exhibit their maximum therapeutic effects. The mitochondria in tumor cells are closely related to the development of tumor. Also, the main cause of clinical failure in antitumor treatment, including multidrug resistance (MDR) and metastasis, are associated with mitochondrial dysfunction. In addition, mitochondria disorders also lead to some other diseases. Therefore, constructing mitochondrial targeted drug delivery systems to regulate mitochondrial functions is necessarily desired. Keywords Mitochondria · Targeted strategies · Drug delivery systems · Antitumor · Mitochondrial-related diseases
Introduction Mitochondria are the main site of ATP production, known as the “power house” of eukaryotic cells. In addition to the vital physiological functions, mitochondria also participate in pathological progression (Lu et al. 2016; Yamada and Harashima 2008). Many studies have demonstrated that mitochondrial dysfunction was closely related to the development of multiple diseases, including diabetes (Lowell and Shulman 2005; Szendroedi et al. 2011), nonalcoholic fatty liver disease (NAFLD) (Sanyal et al. 2001; Wei et al. 2008), cardiovascular and neurodegenerative diseases (Chan 2006), kidney injury (Hallan and Sharma 2016; Hall and Schuh 2016) and cancer (Wallace 2012; Fulda et al. * Yuan Huang [email protected] 1
Key Laboratory of Drug Targeting and Drug Delivery System (Ministry of Education), West China School of Pharmacy, Sichuan University, No. 17, Block 3, South Renmin Road, Chengdu 610041, People’s Republic of China
2010; Battogtokh et al. 2018). Therefore, mitochondria are emerged as an attractive target for diseases treatment. Mitochondria with a double-membrane structure are composed of outer membrane (OMM), interspace membrane (ISM), inner mitochondrial membrane (IMM), and matrix (Lu et al. 2016). The matrix contains DNA
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