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|Title:||On the mechanisms of internalization and intracellular delivery mediated by pH-sensitive liposomes||Authors:||Simões, Sérgio
Pedroso de Lima, Maria C.
|Keywords:||Intracellular delivery; pH-sensitive liposome; Dioleoylphosphatidylethanolamine; Differentiated THP-1 cell; Flow cytometry; Amphiphilic stabilizer||Issue Date:||2001||Citation:||Biochimica et Biophysica Acta (BBA) - Biomembranes. 1515:1 (2001) 23-37||Abstract:||We investigated the molecular mechanisms by which pH-sensitive liposomes surpass the cytoplasmic and endosomal membranes to deliver their aqueous contents into the cytoplasm. Various liposome formulations were evaluated for their efficacy to mediate intracellular delivery of encapsulated material, including a novel sterically stabilized pH-sensitive formulation ((DOPE:CHEMS:DSPE-PEG2000 (6:4:0.3)) that was previously developed in our laboratories. In an attempt to fully characterize the nature of liposome-cell interactions different approaches based on a dual-labeling fluorescence assay were used. Our results indicate that the efficacy of interaction of pH-sensitive liposomes, both plain and sterically stabilized, with cells is strongly determined by the inclusion of DOPE in their composition, independently of the type of the amphiphilic stabilizer used. In fact, DOPE-containing liposomes shown to be non-pH sensitive by biophysical assays, mediated cytoplasmic delivery of their contents as efficiently as well known pH-sensitive formulations (e.g. DOPE:CHEMS). However, among the different formulations studied, DOPE:CHEMS liposomes were those exhibiting the highest extent of cell association. Moreover, our results with cells pretreated with metabolic inhibitors or lysosomotropic agents clearly indicate that DOPE-containing liposomes are internalized essentially by endocytosis and that acidification of the endosomes is not the only mechanism involved in the destabilization of the liposomes inside the cell.||URI:||http://hdl.handle.net/10316/5796||Rights:||openAccess|
|Appears in Collections:||FFUC- Artigos em Revistas Internacionais|
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