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

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.

Identiferoai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:583556
Date January 2005
CreatorsAl-Taei, Saly
PublisherCardiff University
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Sourcehttp://orca.cf.ac.uk/55383/

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