Optimisation of folate-mediated liposomal encapsulated arsenic trioxide for treating HPV-positive cervical cancer cells in vitro

Akhtar, Anam, Ghali, Lucy, Wang, Scarlet, Bell, Celia M., Li, Dong and Wen, Xuesong (2019) Optimisation of folate-mediated liposomal encapsulated arsenic trioxide for treating HPV-positive cervical cancer cells in vitro. International Journal of Molecular Sciences, 20 (9). ISSN 1422-0067

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High-risk human papilloma virus (HPV) infection is directly associated with cervical cancer development. Arsenic trioxide (ATO), despite inducing apoptosis in HPV-infected cervical cancer cells in vitro, has been compromised by toxicity and poor pharmacokinetics in clinical trials. Therefore, to improve ATO’s therapeutic profile for HPV-related cancers, this study aims to explore the effects of length of ligand spacers of folate-targeted liposomes on the efficiency of ATO delivery to HPV-infected cells. Fluorescent ATO encapsulated liposomes with folic acid (FA) conjugated to two different PEG lengths (2000 Da and 5000 Da) were synthesised, and their cellular uptake was examined for HPV-positive HeLa and KB and HPV-negative HT-3 cells using confocal microscopy, flow cytometry, and spectrophotometer readings. Cellular arsenic quantification and anti-tumour efficacy was evaluated through inductively coupled plasma-mass spectrometry (ICP-MS) and cytotoxicity studies, respectively. Results showed that liposomes with a longer folic acid-polyethylene glycol (FA-PEG) spacer (5000 Da) displayed a higher efficiency in targeting folate receptor (FR) + HPV-infected cells without increasing any inherent cytotoxicity. Targeted liposomally delivered ATO also displayed superior selectivity and efficiency in inducing higher cell apoptosis in HPV-positive cells per unit of arsenic taken up than free ATO, in contrast to HT-3. These findings may hold promise in improving the management of HPV-associated cancers.

Item Type: Article
Additional Information: Article number = 2156 ** From MDPI via Jisc Publications Router ** History: accepted 29-04-2019; pub-electronic 30-04-2019.
Keywords (uncontrolled): arsenic trioxide (ATO), liposome, targeted drug delivery, cervical cancer, human papilloma virus (HPV), folate conjugation
Research Areas: A. > School of Science and Technology > Natural Sciences
Item ID: 26531
Notes on copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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SWORD Depositor: Jisc Publications Router
Depositing User: Jisc Publications Router
Date Deposited: 02 May 2019 07:41
Last Modified: 02 May 2019 09:11
URI: https://eprints.mdx.ac.uk/id/eprint/26531

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