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Title: Targeting of sterically stabilised pH-sensitive liposomes to human T-leukaemia cells
Authors: Fonseca, Cristina 
Moreira, João N. 
Ciudad, Carlos J. 
Pedroso de Lima, Maria C. 
Simões, Sérgio 
Keywords: Nanotechnology; pH-sensitive liposomes; Targeting; Transferrin; Human T-leukaemia cells; Cancer therapy
Issue Date: 2005
Citation: European Journal of Pharmaceutics and Biopharmaceutics. 59:2 (2005) 359-366
Abstract: The main aim of this work was to develop novel targeted sterically stabilised pH-sensitive liposomes tailored to promote efficient intracellular delivery of therapeutic molecules into human T-leukaemia cells. Our results indicate that the targeting moiety (thiolated transferrin) was successfully coupled to the distal reactive maleimide terminus of poly(ethylene glycol)-phospholipid conjugates incorporated in the liposomal bilayer. Results from atomic force microscopy studies, performed to characterise vesicle surface topology, indicated that, to a certain extent, thiolated transferrin has the ability to associate in a non-specific manner with the lipid membrane of pegylated liposomes. This is an issue not commonly reported in the literature but which is crucial to demonstrate the targeting proof of principle. Nevertheless, fluorimetric studies together with confocal microscopy clearly demonstrate that liposomes bearing covalently coupled transferrin associate more extensively to human T-leukaemia cells in vitro than non-targeted liposomes. Cell mechanistic studies indicate that targeted liposomes bind specifically to transferrin receptors and are internalised via receptor-dependent endocytotic pathway. In addition, the biophysical features exhibited by the developed liposomes, namely their ability to promote pH-triggered cytoplasmic delivery of loaded material, make them promising delivery systems for in vivo targeting of therapeutic molecules to tumours.
DOI: 10.1016/j.ejpb.2004.08.012
Rights: openAccess
Appears in Collections:FFUC- Artigos em Revistas Internacionais

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