Mitochondrial Delivery of Bongkrekic Acid Using a MITO-Porter Prevents the Induction of Apoptosis in Human HeLa Cells

The fact that mitochondrial dysfunction has been implicated in a variety of human diseases suggests that they would be expected as a target organelle for these diseases. Bongkrekic acid (BKA) is a chemical that functions as a ligand of the adenine nucleotide translocator and is known to potently inh...

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Published in:Journal of pharmaceutical sciences 2013-03, Vol.102 (3), p.1008-1015
Main Authors: Yamada, Yuma, Nakamura, Kohei, Furukawa, Ryo, Kawamura, Eriko, Moriwaki, Takuya, Matsumoto, Kenji, Okuda, Katsuhiro, Shindo, Mitsuru, Harashima, Hideyoshi
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - administration & dosage
Anti-Bacterial Agents - pharmacology
antiapoptotic effect
Apoptosis - drug effects
biomaterials
bongkrekic acid
Bongkrekic Acid - administration & dosage
Bongkrekic Acid - pharmacology
cell culture
Drug Delivery Systems
HeLa Cells
Humans
liposomes
Liposomes - chemistry
Liposomes - metabolism
MITO- Porter
mitochondria
Mitochondria - drug effects
Mitochondria - metabolism
mitochondrial medicine
nanotechnology
targeted drug delivery
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Summary:The fact that mitochondrial dysfunction has been implicated in a variety of human diseases suggests that they would be expected as a target organelle for these diseases. Bongkrekic acid (BKA) is a chemical that functions as a ligand of the adenine nucleotide translocator and is known to potently inhibit the mitochondrial permeability transition that is associated with apoptosis. Thus, delivering it to mitochondria would be an innovative therapy for the treatment of mitochondrial diseases that are largely associated with apoptosis. Here, we report on the use of a MITO-Porter, an innovative nanocarrier for mitochondrial delivery via mitochondrial membrane fusion, for delivering BKA to mitochondria. We first constructed a BKA-MITO-Porter, in which BKA is contained in lipid envelopes of a MITO-Porter. We then confirmed that the BKA–MITO-Porter was efficiently internalized into cells and is delivered to mitochondria, similar to a conventional MITO-Porter. Moreover, we evaluated the antiapoptosis effect of the BKA–MITO-Porter in HeLa cells by measuring caspase 3/7 activity. The findings confirmed that the BKA–MITO-Porter showed a strong antiapoptosis effect compared with naked BKA. The results reported here demonstrate its potential for the use in therapies aimed at mitochondrial diseases, as a mitochondrial medicine candidate. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1008–1015, 2013
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.23442