Antibody-conjugated vitamin e-derived liposomes for targeted gene transfer

Bhattacharya, S and Kamra, M and Maiti, B and Saha, P and Karande, AA (2020) Antibody-conjugated vitamin e-derived liposomes for targeted gene transfer. In: ACS Applied Bio Materials . (In Press)

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Abstract

Construction of a vitamin E-based liposomal biomaterial and its ability to deliver therapeutic genes selectively across liver cancer cells are demonstrated herein. In humans, liver regulates the levels of α-tocopherol, i.e., vitamin E, and hepatic cells carry the machinery for its transport. To exploit the presence of tocopherol transport protein, we have selected an efficient gene transfecting α-tocopherol-based twin lipid bearing a hydroxyethylated headgroup and octamethylene spacer (TH8S) for liposome formation. Also, based on the abundancy of the low-density lipoprotein receptor (LDLr) on the cellular surface in the case of hepatocellular carcinoma, anti-LDLr monoclonal antibody is used to confer the targeting ability to liposomes. A facile thiol- maleimide click chemistry is used for antibody decoration on the liposomal surface. Selective delivery of reporter and therapeutic genes (GFP and p53) to cells of hepatic origin was observed using anti-LDLr-tagged TH8S liposomes. Cellular internalization by receptor-mediated endocytosis renders the bioconjugate highly specific as well as highly efficient. Compatibility of the designed material with human blood points to its safety of use in systemic circulation thereby highlighting its in vivo potential. Thus, we report here a versatile biomaterial derived from an essential vitamin that promises potential for targeted suicidal gene therapy. © 2020 American Chemical Society. All rights reserved.

Item Type:	Journal Article
Publication:	ACS Applied Bio Materials
Publisher:	American Chemical Society
Additional Information:	Copyright to this article belongs to American Chemical Society
Keywords:	Gene therapy; Gene transfer; Machinery; Molecular biology; Monoclonal antibodies, Cellular internalization; Hepatocellular carcinoma; Liposome formation; Liver cancer cells; Low density lipoprotein receptors; Receptor-mediated endocytosis; Systemic circulation; Transport proteins, Liposomes
Department/Centre:	Division of Biological Sciences > Biochemistry Division of Chemical Sciences > Organic Chemistry
Date Deposited:	08 Jan 2021 11:07
Last Modified:	08 Jan 2021 11:07
URI:	http://eprints.iisc.ac.in/id/eprint/67547

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