title: Therapeutic Potential of Delivering Arsenic Trioxide into HPV-Infected Cervical Cancer Cells Using Liposomal Nanotechnology.
abstract: 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.
authors.affiliation: Centre for Investigative and Diagnostic Oncology, Middlesex University, London, NW4 4BT, UK.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Centre for Investigative and Diagnostic Oncology, Middlesex University, London, NW4 4BT, UK.|Department of Natural Sciences, School of Science and Technology, Middlesex University, The Burroughs, NW4 4BT, UK.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Centre for Investigative and Diagnostic Oncology, Middlesex University, London, NW4 4BT, UK.|Department of Natural Sciences, School of Science and Technology, Middlesex University, The Burroughs, NW4 4BT, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Ghali
authors.affiliation: Jiangsu Key Laboratory for Organic Electronics and Information Displays (KLOEID), Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications (NJUPT), 9 Wenyuan Road, Nanjing, 210046, People's Republic of China.
authors.forename: Ruidong
authors.initials: R
authors.lastname: Xia
authors.affiliation: Department of Natural Sciences, School of Science and Technology, Middlesex University, The Burroughs, NW4 4BT, UK.
authors.forename: Leonardo P
authors.initials: LP
authors.lastname: Munoz
authors.affiliation: Department of Natural Sciences, School of Science and Technology, Middlesex University, The Burroughs, NW4 4BT, UK.
authors.forename: Hemda
authors.initials: H
authors.lastname: Garelick
authors.affiliation: Department of Natural Sciences, School of Science and Technology, Middlesex University, The Burroughs, NW4 4BT, UK.
authors.forename: Celia
authors.initials: C
authors.lastname: Bell
authors.affiliation: Centre for Investigative and Diagnostic Oncology, Middlesex University, London, NW4 4BT, UK. x.wen@mdx.ac.uk.|Department of Natural Sciences, School of Science and Technology, Middlesex University, The Burroughs, NW4 4BT, UK. x.wen@mdx.ac.uk.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Wen
keywords: Apoptosis; Arsenic trioxide; Cervical cancer; Double immunostaining; HPV-E6; Liposomal nanotechnology; Liposome