Combinatorial Therapy: Targeting CD133+ Glioma Stem-like Cells with a Polysaccharide–Prodrug Complex Functionalised Gold Nanocages

Author:

Raveendran Sreejith1ORCID,Giram Amit2,Elmi Mehrnaz2,Ray Santanu3ORCID,Ireson Christopher2,Alavijeh Mo2ORCID,Savina Irina N.1ORCID

Affiliation:

1. School of Pharmacy and Biomolecular Sciences, University of Brighton, Moulsecoomb, Lewes Road, Moulsecoomb, Brighton BN2 4GJ, UK

2. Pharmidex Pharmaceutical Services Limited, 167-169 Great Portland Street, Fifth Floor, London W1W 5PF, UK

3. School of Environmental Sciences, University of Brighton, Moulsecoomb, Lewes Road, Moulsecoomb, Brighton BN2 4GJ, UK

Abstract

Cancer treatments are advancing to harness the body’s immune system against tumours, aiming for lasting effects. This progress involves combining potent chemotherapy drugs with immunogens to kill cancer cells and trigger lasting immunity. Developing new prodrugs that integrate both chemotherapy and immune-boosting elements could significantly improve anticancer outcomes by activating multiple mechanisms to kill cancer cells. While bacterial polysaccharides are typically not used in therapy due to their immune-stimulating properties, we propose a safe application of an extremophilic bacterial polysaccharide, Mauran (MR), modified with the anticancer drug 5-fluorouracil (5FU) to create a novel prodrug. This obtained prodrug, chloracetyl-MR-5FU, is specifically targeted using gold nanocages to CD133+ glioma cells. Test results have shown a high encapsulation efficiency of the drug during the polysaccharide modification process; its anticancer activity was demonstrated in vitro and the release of the prodrug was demonstrated in ex vivo studies.

Funder

European Commission

University of Brighton

Publisher

MDPI AG

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