Reduction Responsive Nanovesicles Derived from Novel α-Tocopheryl-Lipoic Acid Conjugates for Efficacious Drug Delivery to Sensitive and Drug Resistant Cancer Cells.
Bioconjug Chem
; 29(2): 255-266, 2018 02 21.
Article
em En
| MEDLINE
| ID: mdl-29268009
ABSTRACT
Two novel α-tocopheryl-lipoic acid conjugates (TL1 and TL2) were synthesized for the anticancer drug, doxorubicin (DOX), delivery. Both conjugates were able to form stable nanovesicles. The critical aggregation concentration (CAC) was determined using 4-(N,N-dimethylamino)cinnamaldehyde (DMACA) as a fluorescence probe. Formation of highly packed nanovesicles was characterized by 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence anisotropy and microviscosity measurements. The morphologies of nanovesicles were visualized by transmission electron microscopy (TEM) and atomic force microscopy (AFM). The response of nanovesicles to reducing environment of cells was probed by the addition of dithiothreitol (DTT), which was followed by the increase in the hydrodynamic diameter under dynamic light scattering (DLS) measurements. The encapsulation efficiency of a commonly used anticancer drug, doxorubicin (DOX), in nanovesicles was found to be â¼60% and â¼55% for TL1 and TL2, respectively (TL1-DOX and TL2-DOX). Also, the cumulative drug (DOX) release from DOX-encapsulated nanovesicles in response to biological reducing agent glutathione (GSH) was â¼50% and â¼40% for TL1-DOX and TL2-DOX, respectively, over a period of 10 h. Both TL1-DOX and TL2-DOX delivered the anticancer drug, doxorubicin (DOX), across the DOX-sensitive and DOX-resistant HeLa (HeLa-DOXR) cells in an efficient manner and significantly more efficaciously than the drug alone treatments, especially in HeLa-DOXR cells. The nanovesicle mediated DOX treatment also showed significantly higher cell death when compared to DOX alone treatment in HeLa-DOXR cells. Blood compatibility of the nanovesicles was supported from clotting time, hemolysis, and red blood cell (RBC) aggregation experiments for their potential in vivo applications. Concisely, we present biocompatible and responsive nanovesicles for efficacious drug delivery to drug-sensitive and drug-resistant cancer cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doxorrubicina
/
Ácido Tióctico
/
Alfa-Tocoferol
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Preparações de Ação Retardada
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Nanocápsulas
/
Antineoplásicos
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
Bioconjug Chem
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Índia