Hepatocellular carcinoma is the most common type of primary liver cancer, which is the second leading cause of cancer deaths in the world. Due to the ineffectiveness of common treatments, recurrence of cancer, nontargeted function and damage to healthy cells, aggressiveness and resistance of cancer cells to these treatments, there is a serious need to find more effective treatments. Drug delivery based on nanotechnology is one of the new therapeutic modalities that causes the targeted delivery of anticancer compounds to the target site (tumor), preventing the oxidation of drugs in biological conditions, increasing the stability of drugs and increasing the dissolution rate of poorly soluble substances in water. Niosomes are one of the common types of nanoparticles in modern drug delivery systems, which are receiving attention nowadays. They have the ability to load hydrophilic and hydrophobic drugs, are biodegradable, have more stability compared to liposomes, have less toxicity and immunogenicity. They are economical and it is easy to prepare and use them. So far, many anticancer compounds have been loaded in niosomes. Linoleic acid (LA) is an essential fatty acid with anticancer properties that has not been loaded into the niosome. Therefore, the purpose of this study is to design, synthesis, characterize the physicochemical properties of niosomes containing linoleic acid and evaluate their effects on hepatocellular carcinoma cells.

LA-loaded niosomes were synthesized using span-60 as an anionic surfactant and cholesterol (1:1) by thin film hydration method. The synthesised niosomes were sonicated for 5 minutes. Their physiochemical features such as size, zeta potential and polydispersity index (PDI) was assessed by zeta sizer (DLS( and morphology of niosomes was evaluated by scanning electron microscope (SEM). Also, entrapment efficiency (EE%) with amicone, release rate with dialysis bag and stability of niosomes were estimated during 30 days. Finally, the toxicity effects of LA-loaded niosomes was evaluated on Hep-3B cells and fibroblasts (HFF) as a normal cell line.

The zeta sizer results showed niosomes had size of 105.7 nm, PDI of 0.271 and -26.1 mV zeta potential. The SEM pictures indicated that niosomes had appropriate morphology with decreased size in comparison to reported size by DLS. Niosomes with EE 74%, released LA slowly and in a sustained manner during 72 hours. The stability findings showed niosomes in 4C0 were more stable than niosomes in 25C0 after 30 days. The MTT assay results indicated that LA-loaded niosomes were more toxic than free LA to cancerous cells. But, they showed no toxic effects on HFF cells.

Niosome is a stable, non-immunogenic, and cost-effective nanoparticle with high drug encapsulation capacity. The results indicate that niosomes containing linoleic acid had good properties and also had a toxic effect on hepatocellular carcinoma cells. Therefore, the use of niosome as a nanocarrier can be a good way to target and destroy cancer cells.