A Novel Drug Delivery System Incorporates a Functional Composite Scaffold Derived from Taxifolin with Potential Cytotoxic and Anticancer Effects on Triple Negative Breast Cancer
Triple-negative breast cancer (TNBC) is characterised by its aggressive nature and poor prognosis. This study examines the anticancer properties of the flavonoid taxifolin and its cytotoxic and genotoxic effects on triple-negative breast cancer (TNBC) and blood cells from healthy individuals and breast cancer patients. Central to this work is the development of a novel taxifolin delivery system via electrospun PCL scaffolds to enhance anticancer and therapeutic efficacy of the drug post-operatively. The Comet assay was utilised to analyse DNA damage and repair in lymphocytes from breast cancer patients versus healthy controls. CCK-8, qPCR and Western Blot were employed to study viability, gene, and protein expression regulation during taxifolin treatment. The process and formulation of the drug-PCL scaffolds were optimised to produce scaffolds with no beadings and optimal fibre structures. Thermal and microscopy analysis indicates no detectable crystals in the scaffold. The results from the experiment using Comet assay indicate that taxifolin significantly protects DNA in both healthy and breast cancer samples, effectively decreasing DNA damage in breast cancer blood samples and showing genotoxicity against TNBC cells. Taxifolin regulates essential molecular pathways, as evidenced by changes in genes (p53, p21, p27,and Bcl-2) using qPCR and protein levels (p53, p27, and Bcl-2) using Western Blot, suggesting its potential in targeted therapy. The optimised taxifolin-PCL electrospun scaffold enhances cell adhesion, reducing cell viability and proliferation of TNBC, underscoring the efficacy of localised taxifolin delivery. This thesis emphasizes the therapeutic potential of a new drug delivery system for more effective treatment of TNBC.
Triple-negative breast cancer (TNBC), Taxifolin, Polycaprolactone (PCL), Electrospun scaffold, Genotoxic, Cytotoxic, Comet assay, QPCR, Western Blot, Electrospinning, Drug delivery, Anticancer therapy
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