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The Interaction of Temozolomide with Blood Components Suggests the Potential Use of Human Serum Albumin as a Biomimetic Carrier for the Drug


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Título :
The Interaction of Temozolomide with Blood Components Suggests the Potential Use of Human Serum Albumin as a Biomimetic Carrier for the Drug
Autor :
Rubio-Camacho, Marta  
Encinar, José Antonio  
Martínez Tomé, María José
Esquembre, Rocío  
Mateo , C. Reyes  
Editor :
MDPI
Departamento:
Departamentos de la UMH::Agroquímica y Medio Ambiente
Fecha de publicación:
2020-07-08
URI :
https://hdl.handle.net/11000/30732
Resumen :
The interaction of temozolomide (TMZ) (the main chemotherapeutic agent for brain tumors) with blood components has not been studied at the molecular level to date, even though such information is essential in the design of dosage forms for optimal therapy. This work explores the binding of TMZ to human serum albumin (HSA) and alpha-1-acid glycoprotein (AGP), as well as to blood cell-mimicking membrane systems. Absorption and fluorescence experiments with model membranes indicate that TMZ does not penetrate into the lipid bilayer, but binds to the membrane surface with very low affinity. Fluorescence experiments performed with the plasma proteins suggest that in human plasma, most of the bound TMZ is attached to HSA rather than to AGP. This interaction is moderate and likely mediated by hydrogen-bonding and hydrophobic forces, which increase the hydrolytic stability of the drug. These experiments are supported by docking and molecular dynamics simulations, which reveal that TMZ is mainly inserted in the subdomain IIA of HSA, establishing -stacking interactions with the tryptophan residue. Considering the overexpression of albumin receptors in tumor cells, our results propose that part of the administered TMZ may reach its target bound to plasma albumin and suggest that HSA-based nanocarriers are suitable candidates for designing biomimetic delivery systems that selectively transport TMZ to tumor cells.
Palabras clave/Materias:
temozolomide (TMZ)
bloodstream components interaction
human serum albumin (HSA)
alpha-1-acid glycoprotein (AGP)
model biomembranes
molecular docking
Área de conocimiento :
CDU: Ciencias puras y naturales: Química
Tipo documento :
application/pdf
Derechos de acceso:
info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
DOI :
ttps://doi.org/10.3390/biom10071015
Aparece en las colecciones:
Artículos Agroquímica y Medio Ambiente



Creative Commons La licencia se describe como: Atribución-NonComercial-NoDerivada 4.0 Internacional.