Tumor Chemosensitization through Oncogene Knockdown Mediated by Unique alpha-Tocopherylated Cationic Geminis

Kamra, Mohini and Maiti, Bappa and Dixit, Akanksha and Karande, Anjali A and Bhattacharya, Santanu (2019) Tumor Chemosensitization through Oncogene Knockdown Mediated by Unique alpha-Tocopherylated Cationic Geminis. In: BIOMACROMOLECULES, 20 (4). pp. 1555-1566.

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Abstract

Herein, siRNA transfection efficiency of a unique set of alpha-tocopherylated gemini lipids has been established in vitro and in vivo. High efficacy of oncogene silencing achieved using the biomacromolecular assembly, formed from siRNA complexes of co-liposomes containing an alpha-tocopherylated gemini lipid, has been utilized for tumor regression via chemosensitization. Delivery studies with the gemini bearing hydroxyethyl headgroup with octamethylene spacer (TH8S) pointed to a higher siRNA transfection efficacy than its analog without hydroxyethyl group (T8S). Owing to p53 upregulation, transfected cells showed enhanced sensitivity to the chemotherapeutic agent, doxorubicin. Studies in murine model revealed significantly low levels of survivin mRNA in xenograft tumors injected with siRNA lipoplexes, leading to effective inhibition of tumor growth and an increase in sensitivity of the tumors toward doxorubicin. These findings enable us to propose the anti-survivin siRNA carrying TH8S co-liposomes as a potent member of cancer management strategies using suicide gene therapy.

Item Type:	Journal Article
Publication:	BIOMACROMOLECULES
Publisher:	AMER CHEMICAL SOC
Additional Information:	The copyright for this article belongs to American Chemical Society
Department/Centre:	Division of Biological Sciences > Biochemistry Division of Chemical Sciences > Organic Chemistry
Date Deposited:	29 Apr 2019 07:43
Last Modified:	29 Apr 2019 07:43
URI:	http://eprints.iisc.ac.in/id/eprint/62548

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