The daunorubicin interplay with mimetic model membranes of cancer cells: A biophysical interpretation

• Tipo: Artigo em Revista Científica Internacional
• Data: 2017

Autores

Alves, AC (Autor) Outra; Ribeiro, D (Autor) Outra; Horta, M (Autor) Outra; Lima, JLFC (Autor) FMUP; Nunes, C (Autor) Outra; Salette Reis (Autor) FFUP

Revista

Título: Biochimica et Biophysica Acta: Biomembranes

Vol. 1859

Páginas: 941-948

ISSN: 0005-2736

Editora: Elsevier

Indexação

ISI Web of Knowledge - 4 Citações

Scopus - 8 Citações

Outras Informações

ID Authenticus: P-00M-PTG

DOI: 10.1016/j.bbamem.2017.01.034

Abstract (EN): The present work aimed to study the interactions between the anticancer drug daunorubicin and lipid membrane mimetic models of cancer cells composed by their most representative classes of phospholipids, with different degrees of complexity. Regarding these anticancer drug-membrane interactions, several biophysical parameters were assessed using liposomes (LUVs) composed of different molar ratios of DMPC, DOPC, DPPS, DOPE and Chol. In this context, daunorubicin's membrane concentration was determined by calculating its partition coefficient (4) between liposomes and water using derivative UV/vis spectrophotometry at 37 degrees C and pH 6.3, a typical tumoral microenvironment. Characterization of the zeta potential of such model membranes, in both the absence and presence of the compound, was accomplished through Electrophoretic Light Scattering (ELS). Fluorescence quenching studies, which determine the location of the drug within the bilayer, were carried out using liposomes labelled with DPH and TMA-DPH, fluorescent probes with known membrane position. Temperature dependent steady-state anisotropy assays were also performed to measure the daunorubicin effect on the membranes' microviscosity. The overall results support that daunorubicin permeation depends on the phospholipid membrane composition and causes alterations in the biophysical properties of the bilayers, namely in the membrane fluidity. The interaction of daunorubicin with the studied phospholipids is mainly driven by electrostatic and hydrophobic interactions. These insights demonstrated that not only membranes can affect daunorubicin accumulation in cells but the compound can alter the properties of membranes. The changes produced by daunorubicin on the lipid structure may constitute an additional mechanism of action, which might lead to modifications in the location and, consequently, the activity of membrane signaling proteins.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 8