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Chimeric nanoparticles for targeting mitochondria in cancer cells
Mitochondrial dysfunction is implicated in myriad diseases, including cancer. Subsequently, targeting mitochondrial DNA (mt-DNA) in cancer cells has emerged as an unorthodox strategy for anti-cancer therapy. However, approaches targeting only one component of the mitochondrial “central dogma” can be...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
RSC
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9419202/ https://www.ncbi.nlm.nih.gov/pubmed/36131756 http://dx.doi.org/10.1039/d1na00644d |
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author | Bajpai, Aman Desai, Nakshi Nayan Pandey, Shalini Shukla, Chinmayee Datta, Bhaskar Basu, Sudipta |
author_facet | Bajpai, Aman Desai, Nakshi Nayan Pandey, Shalini Shukla, Chinmayee Datta, Bhaskar Basu, Sudipta |
author_sort | Bajpai, Aman |
collection | PubMed |
description | Mitochondrial dysfunction is implicated in myriad diseases, including cancer. Subsequently, targeting mitochondrial DNA (mt-DNA) in cancer cells has emerged as an unorthodox strategy for anti-cancer therapy. However, approaches targeting only one component of the mitochondrial “central dogma” can be evaded by cancer cells through various mechanisms. To address this, herein, we have engineered mitochondria-targeting cholesterol-based chimeric nanoparticles (mt-CNPs) consisting of cisplatin, camptothecin, and tigecycline, which can simultaneously impair mt-DNA, mitochondrial topoisomerase I (mt-Top1), and mitochondrial ribosomes. mt-CNPs were characterized as being positively charged, spherical in shape, and 187 nm in diameter. Confocal microscopy confirmed that mt-CNPs efficiently localized into the mitochondria of A549 lung cancer cells within 6 h, followed by mitochondrial morphology damage and the subsequent generation of reactive oxygen species (ROS). mt-CNPs showed remarkable cancer-cell killing abilities compared to free-drug combinations in A549 (lung), HeLa (cervical), and MCF7 (breast) cancer cells. These mitochondria-targeting lipidic chimeric nanoparticles could be explored further to impair multiple targets in mitochondria, helping researchers to gain an understanding of mitochondrial translational and transcriptional machinery and to develop new strategies for cancer therapy. |
format | Online Article Text |
id | pubmed-9419202 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | RSC |
record_format | MEDLINE/PubMed |
spelling | pubmed-94192022022-09-20 Chimeric nanoparticles for targeting mitochondria in cancer cells Bajpai, Aman Desai, Nakshi Nayan Pandey, Shalini Shukla, Chinmayee Datta, Bhaskar Basu, Sudipta Nanoscale Adv Chemistry Mitochondrial dysfunction is implicated in myriad diseases, including cancer. Subsequently, targeting mitochondrial DNA (mt-DNA) in cancer cells has emerged as an unorthodox strategy for anti-cancer therapy. However, approaches targeting only one component of the mitochondrial “central dogma” can be evaded by cancer cells through various mechanisms. To address this, herein, we have engineered mitochondria-targeting cholesterol-based chimeric nanoparticles (mt-CNPs) consisting of cisplatin, camptothecin, and tigecycline, which can simultaneously impair mt-DNA, mitochondrial topoisomerase I (mt-Top1), and mitochondrial ribosomes. mt-CNPs were characterized as being positively charged, spherical in shape, and 187 nm in diameter. Confocal microscopy confirmed that mt-CNPs efficiently localized into the mitochondria of A549 lung cancer cells within 6 h, followed by mitochondrial morphology damage and the subsequent generation of reactive oxygen species (ROS). mt-CNPs showed remarkable cancer-cell killing abilities compared to free-drug combinations in A549 (lung), HeLa (cervical), and MCF7 (breast) cancer cells. These mitochondria-targeting lipidic chimeric nanoparticles could be explored further to impair multiple targets in mitochondria, helping researchers to gain an understanding of mitochondrial translational and transcriptional machinery and to develop new strategies for cancer therapy. RSC 2022-01-18 /pmc/articles/PMC9419202/ /pubmed/36131756 http://dx.doi.org/10.1039/d1na00644d Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Chemistry Bajpai, Aman Desai, Nakshi Nayan Pandey, Shalini Shukla, Chinmayee Datta, Bhaskar Basu, Sudipta Chimeric nanoparticles for targeting mitochondria in cancer cells |
title | Chimeric nanoparticles for targeting mitochondria in cancer cells |
title_full | Chimeric nanoparticles for targeting mitochondria in cancer cells |
title_fullStr | Chimeric nanoparticles for targeting mitochondria in cancer cells |
title_full_unstemmed | Chimeric nanoparticles for targeting mitochondria in cancer cells |
title_short | Chimeric nanoparticles for targeting mitochondria in cancer cells |
title_sort | chimeric nanoparticles for targeting mitochondria in cancer cells |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9419202/ https://www.ncbi.nlm.nih.gov/pubmed/36131756 http://dx.doi.org/10.1039/d1na00644d |
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