Reduction Responsive Nanovesicles Derived from Novel alpha-Tocopheryl-Lipoic Acid Conjugates for Efficacious Drug Delivery to Sensitive and Drug Resistant Cancer Cells

Maiti, Bappa and Kumar, Krishan and Moitra, Parikshit and Kondaiah, Paturu and Bhattacharya, Santanu (2018) Reduction Responsive Nanovesicles Derived from Novel alpha-Tocopheryl-Lipoic Acid Conjugates for Efficacious Drug Delivery to Sensitive and Drug Resistant Cancer Cells. In: BIOCONJUGATE CHEMISTRY, 29 (2). pp. 255-266.

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Abstract

Two novel a-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 micro viscosity 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 similar to 60% and, similar to 55% 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 similar to 50% and similar to 40% 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.

Item Type:	Journal Article
Publication:	BIOCONJUGATE CHEMISTRY
Publisher:	AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
Additional Information:	Copy right for the article belong to AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics Division of Chemical Sciences > Organic Chemistry
Date Deposited:	19 Mar 2018 18:28
Last Modified:	19 Mar 2018 18:28
URI:	http://eprints.iisc.ac.in/id/eprint/59251

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