Effective Delivery of Arsenic Trioxide to HPV-Positive Cervical Cancer Cells Using Optimised Liposomes: A Size and Charge Study.

Anam Akhtar,Xuesong Wen,Celia Bell,Scarlet Wang,Lucy Ghali

doi:10.3390/ijms19041081

Anam Akhtar, Xuesong Wen + Show 3 more

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https://doi.org/10.3390/ijms19041081

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Abstract

Despite the success of arsenic trioxide (ATO) in treating haematological malignancies, its potential to treat solid tumours has not been fully exploited, owing to its dose-limiting toxicity and poor pharmacokinetics. In order to overcome this hurdle, liposomal encapsulation of the drug with different surface charges (neutral, negative, and positive) and sizes (100, 200 and 400 nm) were synthesised and tested on human papilloma virus (HPV)-positive HeLa and HPV-negative HT-3 cervical cancer cell lines. Two epithelial cell lines—human keratinocytes (HK) and human colon cells (CRL-1790)—were used as controls. The synthesised liposomes were tested for their physico-chemical characteristics, drug loading efficiency, and toxicity on the studied cell lines. Neutral liposomes of 100 nm in size were the chosen formulation for delivering ATO into the studied cells, as they showed the least intrinsic cytotoxicity and the highest loading efficiency. The findings demonstrated that the optimised formulation of liposomes was an effective drug delivery method for HPV-infected cervical cancer cells. Furthermore, the toxicity vs. uptake ratio was highest for HeLa cells, while a reduced or minimal toxic effect was observed for non-HPV-infected cervical cancer cells and control cells. These findings may provide a promising therapeutic strategy for effectively managing cervical cancers.

Highlights

Cervical cancer is responsible for 14% of all gynaecological cancers in women, and is linked to high-risk human papilloma virus (HPV) infections [1,2,3]
The mean size and zeta potential of control liposomes were determined by dynamic light scattering (DLS) on a Zetasizer-Nano ZS (Malvern Instruments, Malvern, UK)
After establishing the efficacy of liposomal arsenic trioxide (ATO) in inducing toxicity per unit of arsenic uptake in HPV-positive HeLa cells, we further investigated the effect of liposomal ATO on non-cancerous cells by choosing two cell lines as controls, namely human keratinocytes (HK) and human colon cells (CRL-1790) (Figure 6a,b)

Summary

Introduction

Cervical cancer is responsible for 14% of all gynaecological cancers in women, and is linked to high-risk human papilloma virus (HPV) infections [1,2,3]. Among all of the high-risk HPV subtypes, HPV-16 and HPV-18 account for 70% of all cervical cancers [4,5]. The most common treatment is surgery and/or chemoradiotherapy, which usually results in severe side effects [6,7]. Alternative treatment options that provide better efficacy and specificity with fewer side effects on the surrounding healthy tissues and cells are necessary. An anti-HPV agent that can be taken up by HPV-infected cells is needed because of the crucial role of high-risk HPV infections in the pathogenesis of cervical cancer. The toxic effects on non-HPV-infected surrounding cells and tissues would be reduced

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