Please use this identifier to cite or link to this item: http://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/2490
Title: Nanoparticle-Mediated Mitochondrial Damage Induces Apoptosis in Cancer
Authors: Mallick, Abhik
More, Piyush
Syed, Muhammed
BASU, SUDIPTA
Dept. of Chemistry
Keywords: Cancer
Mitochondria
Nanoparticle
Obatoclax
?-tocopheryl succinate
Apoptosis in Cancer
2016
Issue Date: Jun-2016
Publisher: American Chemical Society
Citation: ACS Applied Materials and Interfaces, 8 (21), 1321-13231.
Abstract: Detouring of conventional DNA damaging anticancer drugs into mitochondria to damage mitochondrial DNA is evolving as a promising strategy in chemotherapy. Inhibiting single target in mitochondria would eventually lead to the emergence of drug resistance. Moreover, targeting mitochondria selectively in cancer cells, keeping them intact in healthy cells, remains a major challenge. Herein, triphenylphosphine (TPP)-coated positively charged 131.6 nm spherical nanoparticles (NPs) comprised of ?-tocopheryl succinate (TOS, inhibitor of complex II in electron transport chain) and obatoclax (Obt, inhibitor of Bcl-2) were engineered. The TOS-TPP-Obt-NPs entered into acidic lysosomes via macropinocytosis, followed by lysosomal escape and finally homed into mitochondria over a period of 24 h. Subsequently, these TOS-TPP-Obt-NPs triggered mitochondrial outer membrane permeabilization (MOMP) by inhibiting antiapoptotic Bcl-2, leading to Cytochrome C release. These TOS-TPP-Obt-NPs mediated mitochondrial damage induced cellular apoptosis through caspase-9 and caspase-3 cleavage to show improved efficacy in HeLa cells. Moreover, TOS-TPP-Obt-NPs induced MOMP in drug-resistant triple negative breast cancer cells (MDA-MB-231), leading to remarkable efficacy, compared to the combination of free drugs in higher drug concentrations. Results presented here clearly stimulate the usage of multiple drugs to perturb simultaneously diverse targets, selectively in mitochondria, as next-generation cancer therapeutics.
URI: http://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/2490
https://doi.org/10.1021/acsami.6b00263
ISSN: 1944-8244
1944-8252
Appears in Collections:JOURNAL ARTICLES

Files in This Item:
There are no files associated with this item.


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