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Supramolecular Pd2L4 self-assembled coordination metallacages for use as drug delivery system for the anti-cancer drug cisplatin

Woods, Benjamin 2019. Supramolecular Pd2L4 self-assembled coordination metallacages for use as drug delivery system for the anti-cancer drug cisplatin. PhD Thesis, Cardiff University.
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Abstract

Cisplatin is a widely used anticancer drug but suffers from drawbacks and limitations, such as severe nephrotoxicity, which are still of great concern. A possible solution to these problems might lie in the optimization of new drug delivery systems able to protect the drug from metabolism (speciation) and to facilitate its uptake in cancer cells. In this context, supramolecular coordination complexes (SCCs), specifically 3D metallacages, hold great promise. These elegant supramolecular structures are well-defined discrete entities formed via self-assembly of bis-monodentate ligands with appropriate metal precursors. Interestingly, the formation of these cages creates a cavity within the structure, which can be exploited for its host-guest properties, thus allowing encapsulation of small molecules. Recently, our group reported on several Pd2L4 (L = 3,5-bis(3-ethynylpyridine)phenyl) metallacages as drug delivery systems for cisplatin. Notably, in vitro studies investigating the antiproliferative effect of coordination cages, with and without cisplatin encapsulated, showed an increased cytotoxicity for the combination cisplatin-cage complex [cage(cisplatin)2] over cisplatin alone in human cancer cells, illustrating their potential as a drug delivery systems. This research project investigated Pd2L4 metallacages as drug delivery systems for cisplatin in greater depth. This will include the exo-functionalisation of the cage architecture with structures such as peptides to improve tumour selectivity and to translocate the blood brain barrier, fluorophores to facilitate in vitro fluorescence microscopy, and to improve the solubility of the cage. Furthermore, the encapsulation of cisplatin in solution will be investigated. DRUG

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Chemistry
Subjects: Q Science > QD Chemistry
Date of First Compliant Deposit: 9 August 2019
Last Modified: 12 Aug 2019 10:02
URI: http://orca-mwe.cf.ac.uk/id/eprint/124833

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