Mitochondrial Delivery of an Anticancer Drug Via Systemic Administration Using a Mitochondrial Delivery System That Inhibits the Growth of Drug-Resistant Cancer Engrafted on Mice
“…We previously developed a MITO-Porter 3-8 a liposomal DDS for delivering cargoes to mitochondria, and reported that such a MITO-Porter system successfully delivered various cargoes including lowmolecular-weight compounds (e.g., anti-cancer drugs, 9 a porphyrintype chemical, 10 coenzyme Q 10 11 ) and macromolecules such as nucleic acids [12][13][14][15] to mitochondria via mitochondrial membrane fusion. We assumed that the MITO-Porter system could accelerate the cellular uptake of vitamin B 1 and would eventually reach the mitochondria.…”
“…We previously developed a MITO-Porter 3-8 a liposomal DDS for delivering cargoes to mitochondria, and reported that such a MITO-Porter system successfully delivered various cargoes including lowmolecular-weight compounds (e.g., anti-cancer drugs, 9 a porphyrintype chemical, 10 coenzyme Q 10 11 ) and macromolecules such as nucleic acids [12][13][14][15] to mitochondria via mitochondrial membrane fusion. We assumed that the MITO-Porter system could accelerate the cellular uptake of vitamin B 1 and would eventually reach the mitochondria.…”
“…Research directed toward the development of nanomedicines based on MITO-Porter technology includes fields such as mitochondrial gene therapy [ [77] , [78] , [79] ], cancer therapy [ [80] , [81] , [82] , [83] , [84] ], ischemic diseases therapy [ 85 , 86 ] and cell therapy [ 87 ]. Our research outcomes regarding validating a mitochondrial gene therapeutic strategy are summarized in the following section, with a particular focus on mitochondrial RNA therapy.…”
Section: Challenge For Mitochondrial Rna Therapy Using a Mitochondriamentioning
Due to the rapid changes that have occurred in the field of drug discovery and the recent developments in the early 21st century, the role of drug delivery systems (DDS) has become increasingly more important. For the past 20 years, our laboratory has been developing gene delivery systems based on lipid-based delivery systems. One of our efforts has been directed toward developing a multifunctional envelope-type nano device (MEND) by modifying the particle surface with octaarginine, which resulted in a remarkably enhanced cellular uptake and improved intracellular trafficking of plasmid DNA (pDNA). When we moved to
in vivo
applications, however, we were faced with the PEG-dilemma and we shifted our strategy to the incorporation of ionizable cationic lipids into our system. This resulted in some dramatic improvements over our original design and this can be attributed to the development of a new lipid library. We have also developed a mitochondrial targeting system based on a membrane fusion mechanism using a MITO-Porter, which can deliver nucleic acids/pDNA into the matrix of mitochondria. After the appearance of antibody medicines, Opdivo, an immune checkpoint inhibitor, has established cancer immunology as the 4th strategy in cancer therapy. Our DDS technologies can also be applied to this new field of cancer therapy to cure cancer by controlling our immune mechanisms. The latest studies are summarized in this review article.
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