Artículo
Macrophage apoptosis using alendronate in targeted nanoarchaeosomes
Jerez, Horacio Emanuel
; Altube, María Julia
; Gándola, Yamila Belén
; Gonzalez, Lorena
; Gonzalez, Marina Cecilia
; Morilla, María José
; Romero, Eder Lilia
Fecha de publicación:
03/2021
Editorial:
Elsevier Science
Revista:
European Journal of Pharmaceutics and Biopharmaceutics
ISSN:
0939-6411
e-ISSN:
1873-3441
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Nanoarchaeosomes are non-hydrolysable nanovesicles made of archaeolipids, naturally functionalised with ligand for scavenger receptor class 1. We hypothesized that nitrogenate bisphosphonate alendronate (ALN) loaded nanoarchaeosomes (nanoarchaeosomes(ALN)) may constitute more efficient macrophage targeted apoptotic inducers than ALN loaded nanoliposomes (nanoliposomes (ALN)). To that aim, ALN was loaded in cholesterol containing (nanoARC-chol(ALN)) or not (nanoARC(ALN)) nanoarchaeosomes. Nanoarchaeosomes(ALN) (220–320 nm sized, ~ −40 mV ξ potential, 38–50 μg ALN/mg lipid ratio) displayed higher structural stability than nanoliposomes(ALN) of matching size and ξ potential, retaining most of ALN against a 1/200 folds dilution. The cytotoxicity of nanoARC(ALN) on J774A.1 cells, resulted > 30 folds higher than free ALN and nanoliposomes(ALN) and was reduced by cholesterol in nanoARC-chol(ALN). Devoid of ALN, nanoARC-chol was non-cytotoxic, exhibited pronounced anti-inflammatory activity on J774.1 cells, strongly reducing reactive oxygen species (ROS) and IL-6 induced by LPS. Nanoarchaeosomes bilayer extensively interacted with serum proteins but resulted refractory to phospholipases. Upon J774A.1 cells uptake, nanoarchaeosomes induced cytoplasmic acid vesicles, reduced the mitochondrial membrane potential by 20–40 % without consuming ATP neither damaging lysosomes and increasing pERK. Refractory to chemoenzymatic attacks, either void or drug loaded, nanoarchaeosomes induced either anti-inflammation or macrophages apoptosis, constituting promising targeted nanovesicles for multiple therapeutic purposes.
Palabras clave:
APOPTOSIS
,
ARCHAEOLIPIDS
,
ENDOCYTOSIS
,
INFLAMMATION
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Licencia
Identificadores
Colecciones
Articulos(INIBIOLP)
Articulos de INST.DE INVEST.BIOQUIMICAS DE LA PLATA
Articulos de INST.DE INVEST.BIOQUIMICAS DE LA PLATA
Articulos(IQUIFIB)
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Articulos de SEDE CENTRAL
Citación
Jerez, Horacio Emanuel; Altube, María Julia; Gándola, Yamila Belén; Gonzalez, Lorena; Gonzalez, Marina Cecilia; et al.; Macrophage apoptosis using alendronate in targeted nanoarchaeosomes; Elsevier Science; European Journal of Pharmaceutics and Biopharmaceutics; 160; 3-2021; 42-54
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