Therapeutic potential of delivering arsenic trioxide into HPV-infected cervical cancer cells using liposomal nanotechnology

Wang, Xiaoyan, Li, Dong ORCID logoORCID:, Ghali, Lucy ORCID logoORCID:, Xia, Ruidong, Pantoja Munoz, Leonardo ORCID logoORCID:, Garelick, Hemda ORCID logoORCID:, Bell, Celia M. ORCID logoORCID: and Wen, Xuesong ORCID logoORCID: (2016) Therapeutic potential of delivering arsenic trioxide into HPV-infected cervical cancer cells using liposomal nanotechnology. Nanoscale Research Letters, 11 (1) , 94. pp. 1-8. ISSN 1931-7573 [Article] (doi:10.1186/s11671-016-1307-y)

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Arsenic trioxide (ATO) has been used successfully to treat acute promyelocytic leukaemia, and since this discovery, it has also been researched as a possible treatment for other haematological and solid cancers. Even though many positive results have been found in the laboratory, wider clinical use of ATO has been compromised by its toxicity at higher concentrations. The aim of this study was to explore an improved method for delivering ATO using liposomal nanotechnology to evaluate whether this could reduce drug toxicity and improve the efficacy of ATO in treating human papillomavirus (HPV)-associated cancers. HeLa, C33a, and human keratinocytes were exposed to 5 μm of ATO in both free and liposomal forms for 48 h. The stability of the prepared samples was tested using inductively coupled plasma optical emission spectrometer (ICP-OES) to measure the intracellular arsenic concentrations after treatment. Fluorescent double immunocytochemical staining was carried out to evaluate the protein expression levels of HPV-E6 oncogene and caspase-3. Cell apoptosis was analysed by flow cytometry. Results showed that liposomal ATO was more effective than free ATO in reducing protein levels of HPV-E6 and inducing cell apoptosis in HeLa cells. Moreover, lower toxicity was observed when liposomal-delivered ATO was used. This could be explained by lower intracellular concentrations of arsenic. The slowly accumulated intracellular ATO through liposomal delivery might act as a reservoir which releases ATO gradually to maintain its anti-HPV effects. To conclude, liposome-delivered ATO could protect cells from the direct toxic effects induced by higher concentrations of intracellular ATO. Different pathways may be involved in this process, depending on local architecture of the tissues and HPV status.

Item Type: Article
Research Areas: A. > School of Science and Technology > Natural Sciences
Item ID: 19007
Notes on copyright: © 2016 Wang et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
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Depositing User: Hemda Garelick
Date Deposited: 11 Mar 2016 11:26
Last Modified: 29 Nov 2022 21:21

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