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Title: | Supramolecular self-assembly of triazine-based small molecules: targeting the endoplasmic reticulum in cancer cells |
Authors: | GHOSH, CHANDRAMOULI NANDI, ADITI Basu, Sudipta Dept. of Chemistry |
Keywords: | Nanoparticle Melamine DNA Mitochondria Peptide Trafficking Chemistry Apoptosis Autophagy Efficacy TOC-MAR-2019 2019 |
Issue Date: | Jan-2019 |
Publisher: | Royal Society of Chemistry |
Citation: | Nanoscale, 11(7), 3326-3335. |
Abstract: | The endoplasmic reticulum (ER) is one of the most important organelles controlling myriads of cellular functions including protein folding/misfolding/unfolding, calcium ion homeostasis and lipid biosynthesis. Subsequently, due to its functional dysregulation in cancer cells, it has emerged as an interesting target for anti-cancer therapy. However, specific targeting of the ER in cancer cells remains a major challenge due to the lack of ER-selective chemical tools. Furthermore, for performing multiple cellular functions the ER is dependent on the nucleus through complicated cross-talk. Herein, we have engineered a supramolecular self-assembled hexameric rosette structure from two small molecules: tri-substituted triazine and 5-fluorouracil (5-FU). This rosette structure consists of an ER-targeting moiety with a fluorescence tag, an ER-stress inducer and a nuclear DNA damaging drug simultaneously, which further self-assembled into an ER-targeting spherical nano-scale particle (ER-NP). These ER-NPs internalized into HeLa cervical cancer cells by macropinocytosis and specifically localized into the ER to induce ER stress and DNA damage leading to cell death through apoptosis. Interestingly, ER-NPs initiated autophagy, inhibited by a combination of ER-NPs and chloroquine (CQ) to augment cancer cell death. This work has the potential to exploit the concept of supramolecular self-assembly into developing novel nano-scale materials for specific sub-cellular targeting of multiple organelles for future anti-cancer therapy. |
URI: | http://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/2386 https://doi.org/10.1039/c8nr08682f |
ISSN: | 2040-3364 2040-3372 |
Appears in Collections: | JOURNAL ARTICLES |
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