Studies on the roles of endocytic pathways in drug delivery and resistance in leukaemia cells

Al-Taei, Saly 2005. Studies on the roles of endocytic pathways in drug delivery and resistance in leukaemia cells. PhD Thesis, Cardiff University.

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Abstract

This study then focused on protein transduction domains (PTD), such as the HIV-Tat and octaarginine, which have shown great promise as vectors for drug delivery and have demonstrated abilities to bypass drug transporters thereby increasing drug efficacy. However their mechanism of entry and eventual cellular fate is much debated in the literature. KG1a and K562 cells were found to be good models for studying the cellular dynamics of fluorescently conjugated PTD as their suspension status minimised background fluorescence resulting from non-specific binding of fluorescent peptides to tissue culture plastic. Immunofluorescence microscopy and flow cytometry implicates a predominantly endocytic mechanism of uptake for these peptides and their final cellular distribution is indicative of late endosomes and lysosomes. Their cellular dynamics suggests they may be able to bypass conventional MDR processes, making them ideal for the circumvention of both transporter mediated drug exclusion and drug sequestration.

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Pharmacy
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RM Therapeutics. Pharmacology
Date of First Compliant Deposit:	30 March 2016
Last Modified:	29 Jun 2022 12:56
URI:	https://orca.cardiff.ac.uk/id/eprint/55383

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