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

Article

Akhtar, A., Ghali, L., Wang, S., Bell, C., Li, D. and Wen, S. 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), pp. 1-20. https://doi.org/10.3390/ijms20092156
TypeArticle
TitleOptimisation of folate-mediated liposomal encapsulated arsenic trioxide for treating HPV-positive cervical cancer cells in vitro
AuthorsAkhtar, A., Ghali, L., Wang, S., Bell, C., Li, D. and Wen, S.
Abstract

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.

Keywordsarsenic trioxide (ATO); liposome; targeted drug delivery; cervical cancer; human papilloma virus (HPV); folate conjugation
PublisherMDPI
JournalInternational Journal of Molecular Sciences
ISSN1661-6596
Electronic1422-0067
Publication dates
Online30 Apr 2019
Print01 May 2019
Publication process dates
Deposited02 May 2019
Accepted29 Apr 2019
Output statusPublished
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© 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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This article belongs to the Special Issue Nanotechnology in Cancer Treatment

Digital Object Identifier (DOI)https://doi.org/10.3390/ijms20092156
Web of Science identifierWOS:000469753500103
LanguageEnglish
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