Does the lipid membrane composition of arsonoliposomes affect their anticancer activity? A cell culture study

Abstract

Sonicated arsonoliposomes were prepared using arsonolipid with palmitic acid acyl chain (C16), mixed with phosphatidylcholine (PC)-based or 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)-based, and cholesterol (Chol) with C16/DSPC/Chol 8:12:10 molar ratio. PEG-lipid (1,2-distearoyl-sn-glycero-3-phosphoethanolamine conjugated to polyethylenoglycol 2000) containing vesicles (PEGylated-arsonoliposomes; PC-based and DSPC-based) were also prepared. The cytotoxicity of these arsonoliposomes towards different cancer cells (human promyelocytic leukaemia NB4, Prostatic cancer PC3, human breast adenocarcinoma MDA-MB-468, human T-lymphocyte (MT-4) and also towards human umbilical vein endothelial cells (HUVECs) was evaluated by calculating the arsonoliposome-induced growth inhibition of the cells by the MTT assay. IC-50 values were interpolated from cell number/arsonoliposome concentration curves. The results reveal that all types of arsonoliposomes evaluated significantly inhibit the growth of most of the cancer cells studied (PC3, NB4, MT4) with the exception of the MDA-MB-468 breast cancer cells which were minimally affected by arsonoliposomes; in some cases even less than HUVEC. Nevertheless, for the same cell type the differences between the different types of arsonoliposomes were significant but not proportional to their stability, indicating that the formation of arsonoliposomes with very stable membranes is not a problem for their anticancer activity. Thereby it is concluded that arsonoliposome composition should be adjusted in accordance to their in vivo kinetics and the desired, for each specific application, biodistribution of As and/or encapsulated drug.

Preparation, Physicochemical Properties, and In Vitro Toxicity towards Cancer Cells of Novel Types of Arsonoliposomes

“…In fact, the addition of TREG in liposomes was observed to confer an increase of vesicle mean diameter and PDI, compared to the corresponding liposomes without TREG; vesicle mean diameter was increased by 10% in the case of LIPs, and ~40% in the case of ARSLs, while PDI values were increased by 127% and 49%, respectively. All results are in good correlation with previously reported values [6,9,[18][19][20].…”

“…The two most important drawbacks are their low toxicity towards some cancer types, and their-up-to-date-inability to overcome the BBB. Indeed, while being highly toxic towards some cancer cell types, such as human leukemia cells (NB4 and HL60), prostatic cancer PC3 cells, and rat brain glioma C6 cells, ARSL did not exhibit the same high toxicity for other cancer cells, such as human breast adenocarcinoma MDA-MB-468 cells, and rat pituitary tumor GH3 cells [5,6]. Additionally, arsenic was not detected in the brain of animals injected with ARSL, in all the cases of ARSL which were studied in vivo [10,11], thus posing an interesting challenge for further exploitation.…”

“…Arsonoliposomes (ARSL) constitute a particular class of liposomes, which are consisted of mixtures of arsonolipids, phospholipids, and cholesterol [2,3]. Nanosized ARSL demonstrate high toxicity against specific cancer cells, while being substantially less toxic towards normal cells, as proven by in vitro [4][5][6] and in vivo studies [7].…”

Organic Arsenicals as Functional Motifs in Polymer and Biomaterials Science

“…Thus far, anticancer activity of arsonoliposomes has only been evaluated in vitro with particular focus on the effects of the arsonolipid components and the overall liposome composition . Activity has been measured against two “normal” cell lines (HUVEC, RAME) and a range of cancer cells with conventional phospholipid analogues employed as As‐free controls . In line antiparasitic activity, unformulated arsonolipids were not active .…”

“…[146] Activity has been measured against two "normal" cell lines (HUVEC, RAME) and a range of cancer cells with conventional phospholipid analogues employed as As-free controls. [146,147] In line antiparasitic activity, unformulated arsonolipids were not active. [131] Conversely, the preliminary results relating to all arsonoliposomes studied validate the working hypothesis that the presence of arsenic in the vesicle membrane activates arsonoliposomes against cancer cells to much greater extent than "normal" cells (e.g., IC 50 HL-60 = 0.85 × 10 −6 m; IC 50 HUVEC = 253 × 10 −6 m).…”