Optimisation of Folate-Mediated Liposomal Encapsulated Arsenic Trioxide for Treating HPV-Positive Cervical Cancer Cells In Vitro

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.

Delivery of Arsenic Trioxide by Multifunction Nanoparticles To Improve the Treatment of Hepatocellular Carcinoma

“…The system was constructed by loading ATO into the cavity of the spheres and coupling microwave (MWA)-sensitive intelligent switch and the targeting molecule on the surface to structure the system of TPP-PCM-ATO@ZrO 2 (abbreviated as TPA@ZrO 2 ). The drug loading efficiency was improved to 54.5% compared with the 25% of liposome in the previous study . Through a series of in vitro and in vivo experiments using the HepG2 cell line and a mouse H22 subcutaneous tumor model, we demonstrated that ATO could be accurately released in a controlled manner in targeted lesions and accumulated to a lethal dose.…”

Arabidopsis thimet oligopeptidases are redox-sensitive enzymes active in the local and systemic plant immune response

“…The concentration of ions (Zn(II), Cu(II), Ni(II), Co(II), Mn(II)) in purified TOPs proteins was determined using an inductively coupled plasma–mass spectrophotometer (ICP-MS) (PerkinElmer SCIEX, ELAN DRC II), which has a limit of quantification of 1 μg/L, as described in ( 91 , 92 ).…”

Mineral medicine: from traditional drugs to multifunctional delivery systems

“…Cervical cancer is a common malignant tumor of the female reproductive system with a high incidence [ 64 ]. There are 500,000 new cases annually in the world.…”

“…Therefore, Akhtar utilized ICP-OES for the quantitative analysis of arsenic. Figure 7 G, H show that neutral liposomes of 100 nm were the highest drug loading rate, which was 24.2%As/P (± 0.848) [ 64 ]. In addition, the cytotoxicity test showed that neutral liposomes were the least toxic.…”

“… Copyright 2013, American Chemical Society. G The drug loading rate of synthetic liposomes was determined by inductively coupled plasma optical emission spectrometry (ICP-OES) at different particle sizes and ( H ) different charges [ 64 ]. Copyright 2019, MDPI …”