Please use this identifier to cite or link to this item: http://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/2386
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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