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

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.

Liposomal formulations of carboplatin injected by convection-enhanced delivery increases the median survival time of F98 glioma bearing rats

“…With our liposomal formulations, the highest encapsulation of carboplatin was obtained with the cationic pegylated formulation L4, which reached a concentration similar to that previously reported by Zhang et al [ 38 ]. Our results also support the hypothesis that higher drug loading can be obtained with positive liposome compared to those with a negative charge [ 39 , 40 ], which can be further increased by adding PEG [ 40 ].…”

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

“…The delivering capacity depends on the structure and composition of the nanoparticles [42,43]. In order to optimize an ATO drug nanocarrier for targeting HPV-infected cervical cells, we firstly optimised ATO encapsulating liposomes, with respect to size and charge, for use as delivery vehicles for our target cells [9]. The second parameter, targeting specificity, is mainly determined from the choice of the ligand and how it interacts with the off-target molecules and cells [20].…”

“…Further studies have indicated that HPV infection might also be responsible for a subset of anal, vulvar, vaginal, penile, upper respiratory-digestive tract, and head and neck cancers [5,6,7,8]. Therefore, targeting HPV infection has become a priority in managing HPV-associated cancers, and an anti-HPV agent that can specifically be taken up by HPV-infected cells is ideally required to enhance treatment and minimise off-target toxicity to surrounding non-HPV-infected cells and tissues [9].…”

Preparation and characterization of erythrocyte membrane cloaked PLGA/arsenic trioxide nanoparticles and evaluation of theirin vitroanti-tumor effect

“…Some materials have been found to facilitate the controlled release of ATO, avoid severe toxicity and reduce side effects. 9 Sheldon 10 used ATO/magnetic nanoparticle (MZF) thermosensitive magnetoliposomes to explore the way in which inorganic arsenic inhibits cell cycle progression through the E2F1-retinoblastoma protein (pRB) as well as its application in cancer therapy. Jadhav et al 11 synthesized dimercaptosuccinic acid (DMSA)/chitosan for coating ATO nanoparticles to study their in vitro antiproliferative activity along with their mechanism of action on LNCaP and PC-3 cell lines.…”