@Article{IPB-384,
author = {Predarska, I. and Saoud, M. and Morgan, I. and Eichhorn, T. and Kaluđerović, G. N. and Hey-Hawkins, E.},
title = {{Cisplatin−cyclooxygenase inhibitor conjugates, free and immobilised in mesoporous silica SBA-15, prove highly potent against triple-negative MDA-MB-468 breast cancer cell line}},
year = {2022},
pages = {857–869},
journal = {Dalton Trans.},
doi = {10.1039/d1dt03265h},
url = {https://doi.org/10.1039/D1DT03265H},
volume = {51},
abstract = {For the development of anticancer drugs with higher activity and reduced
 toxicity, two approaches were combined: preparation of platinum(IV) complexes exhibiting higher stability compared to their platinum(II)
 counterparts and loading them into mesoporous silica SBA-15 with the 
aim to utilise the passive enhanced permeability and retention (EPR) 
effect of nanoparticles for accumulation in tumour tissues. Three 
conjugates based on a cisplatin scaffold bearing the anti-inflammatory 
drugs naproxen, ibuprofen or flurbiprofen in the axial positions (1, 2 and 3, respectively) were synthesised and loaded into SBA-15 to afford the mesoporous silica nanoparticles (MSNs) SBA-15|1, SBA-15|2 and SBA-15|3.
 Superior antiproliferative activity of both free and immobilised 
conjugates in a panel of four breast cancer cell lines (MDA-MB-468, 
HCC1937, MCF-7 and BT-474) with markedly increased cytotoxicity with 
respect to cisplatin was demonstrated. All compounds exhibit highest 
activity against the triple-negative cell line MDA-MB-468, with 
conjugate 1 being the most potent. However, against MCF-7 and BT-474 cell lines, the most notable improvement was found, with IC50
 values up to 240-fold lower than cisplatin. Flow cytometry assays 
clearly show that all compounds induce apoptotic cell death elevating 
the levels of both early and late apoptotic cells. Furthermore, 
autophagy as well as formation of reactive oxygen species (ROS) and 
nitric oxide (NO) were elevated to a similar or greater extent than with
 cisplatin.}    
}