File Download

There are no files associated with this item.

  • Find it @ UNIST can give you direct access to the published full text of this article. (UNISTARs only)
Related Researcher

유자형

Ryu, Ja-Hyoung
Supramolecular Nanomaterials Lab.
Read More

Views & Downloads

Detailed Information

Cited time in webofscience Cited time in scopus
Metadata Downloads

Mitochondria Localized Polymerization for New Cancer Therapy

Author(s)
Ryu, Ja-Hyoung
Issued Date
2018-10-25
URI
https://scholarworks.unist.ac.kr/handle/201301/80700
Citation
AVS 65th International Symposium & Exhibition
Abstract
Recently, targeting mitochondria, the vital organelle for cell survival, as it plays a central role in energy production and apoptotic pathways, has been recognized as an efficient strategy in different therapeutic techniques by disturbing the normal function. Specifically, the conjugation of drug to triphenylphosphonium (TPP), a lipophilic cation, enables its accumulation into the mitochondria of cancer cells more than ~10 times greater than into normal cells as the mitochondrial membrane potentials (~ -220 mV) of cancer cells exhibits more negative charge than that of normal cells (~ -160 mV). The conjugation of TPP with bioactive molecules (e.g. small molecules and peptides) thus would provide a promise approach to target and disrupt the mitochondria of cancer cells, enhancing the efficacy of cancer chemotherapy. Recently, we reported that the supramolecular polymerization of dipeptide inside the mitochondria induced the dysfunction of mitochondria by disrupting the membrane, resulting in the selective apoptosis of cancer cells. Due to the more negative mitochondria membrane potentials in cancer cells compared to normal cells, the TPP-conjugated molecules highly accumulated in the cancer cells and induced the self-assembled structures.

In addition, we describe a mitochondria-targeting biomineralization system that favorably can induce silicification and consequent apoptosis of various cancer cells. The biomineralization system features triphenylphosphonium (TPP) and triethoxysilane (mineralization monomer). The TPP enabled its accumulation into the mitochondria of cancer cells more than 7 times, compared with normal cell. Very intriguingly, the silicification of the triethoxysilane moiety to form biomierals in cancerous mitochondria results in apoptosis thorough mitochondria dysfunction, while there is no toxic effect into normal cell at the same concentration. Furthermore, this system efficiently inhibits the tumor growth of the mouse xenograft cancer model, which is very interesting and efficient anti-cancer therapy with simple molecular design. These results provide a new insight into the use of the mitochondrial targeting molecules for the regulation of cellular functions and a therapeutic approach
Publisher
American Vacuum Society

qrcode

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.