Search Results (3)

Arsonolipids represent a class of arsenic-containing compounds with interesting biological properties either as monomers or as nanostructure forming components, such as arsonoliposomes that possess selective anticancer activity as proven by in vitro and in vivo studies. In this work, we describe, for the first time, the synthesis of novel arsono-containing lipids where the alkyl groups are connected through stable ether bonds. It is expected that this class of arsonolipids, compared with the corresponding ester linked, will have higher chemical stability. To accomplish this task, a new methodology of general application was developed, where a small arsono compound, 2-hydroxyethylarsonic acid, when protected with thiophenol, can be used in an efficient and simple way as a building block for the synthesis of arsono-containing lipids as well as other arsono-containing biomolecules. Thus, besides the above-mentioned arsonolipid, an arsono cholesterol derivative was also obtained. Both ether arsonolipid and arsono cholesterol were able to form liposomes having similar physicochemical properties and integrity to conventional arsonoliposomes. Furthermore, a preliminary in vitro anticancer potential assessment of the novel ether arsonolipid containing liposomes against human prostate cancer (PC-3) and Lewis lung carcinoma (LLC) cells showed significant activity (dose- and time-dependent), which was similar to that of the conventional arsonoliposomes (studied before). Given the fact that novel arsonolipids may be more stable compared to the ones used in conventional arsonoliposomes, the current results justify further exploitation of the novel compounds by in vitro and in vivo studies. Full article

Arsonoliposomes (ARSL) constitute a particular class of liposomes that incorporate arsonolipids (ARS) into their membranes. ARSL realize selective toxicity to cancer cells; thus, they are an important tool in the treatment of cancer. Folic acid (FA) is widely used in targeted drug delivery due to its high affinity for the folate receptors that are overexpressed in cancer cell membranes. The aim of our studies was to develop novel triple-negative breast cancer (TNBC)-targeted ARSL by incorporating folic acid-conjugated polyethylene-glycol PEG-lipid (FA-PEG-lipid) into their membrane and loading them with anticancer drug doxorubicin (DOX). ARSL incorporating 0.1 mol% of FA-PEG-lipid were prepared and loaded with DOX, using the active loading protocol. They were characterized for their size distribution, zeta potential and drug entrapment efficiency (%). Their cytotoxic activity towards TNBC cell lines, particularly MDA-MB-231 (epithelial human breast cancer cells) and MCF7 (human breast cancer cells), was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT-assay. The first results demonstrated enhanced toxicity of this novel type of ARSL towards cancer cells, which is particularly interesting and deserves further exploitation. Full article

Arsonoliposomes (ARSL) are liposomes that incorporate arsonolipids (ARS) in their membranes. They have demonstrated significant toxicity towards cancer cells, while being less toxic towards normal cells. In this study, we sought to investigate the possibility to prepare novel types of arsonoliposomes (ARSL) by incorporating a lipidic derivative of curcumin (TREG) in their membrane, and/or by loading the vesicles with doxorubicin (DOX). The final aim of our studies is to develop novel types of ARSL with improved pharmacokinetics/targeting potential and anticancer activity. TREG was incorporated in ARSL and their integrity during incubation in buffer and serum proteins was studied by monitoring calcein latency. After evaluation of TREG-ARSL stability, the potential to load DOX into ARSL and TREG-ARSL, using the active loading protocol, was studied. Loading was performed at two temperatures (40 °C and 60 °C) and different time periods of co-incubation (of empty vesicles with DOX). Calculation of DOX entrapment efficiency (%) was based on initial and final drug/lipid ratios. The cytotoxic activity of DOX-ARSL was tested towards B16F10 cells (mouse melanoma cells), LLC (Lewis Lung carcinoma cells), and HEK-293 (Human embryonic kidney cells). Results show that TREG-ARSL have slightly larger size but similar surface charge with ARSL and that they are both highly stable during storage at 4 °C for 56 d. Interestingly, the inclusion of TREG in ARSL conferred increased stability to the vesicles towards disruptive effects of serum proteins. The active-loading protocol succeeded to encapsulate high amounts of DOX into ARSL as well as TREG-LIP and TREG-ARSL, while the release profile of DOX from the novel liposome types was similar to that demonstrated by DOX-LIP. The cytotoxicity study results are particularly encouraging, since DOX-ARSL were less toxic towards the (normal) HEK cells compared to the two cancer cell-types. Furthermore, DOX-ARSL demonstrated lower toxicities (at all concentrations tested) for HEK cells, compared to that of the corresponding mixtures of free DOX and empty ARSL, while the opposite was true for the cancer cells (in most cases). The current results justify further in vivo exploitation of DOX-ARSL, as well as TREGARSL as anticancer therapeutic systems. Full article