Investigating the effect of trimethyl-chitosan-hyaluronate nanoparticles loaded with anti-STAT-3 and anti-Tim-3 siRNA molecules in 4T1 (breast cancer) and CT26 (colorectal cancer) cancer cells

Abstract

Tim-3 has been introduced as an important checkpoint in the immune system in recent years and is known as an immune suppressive factor in the tumor microenvironment. STAT-3 has also been introduced as one of the important downstream molecules of Tim-3, in addition to its multiple roles in tumorigenesis through different signaling pathways, which plays an essential role in the tumor growth process. Methods: In the present study, we have produced chitosan-lactate nanoparticles for the targeted delivery of Tim-3 and STAT-3 specific siRNA to cancer cells. Results: Chitosan is known as one of the most efficient nanowires to bind to the negative charges of the cell membrane and penetrate into the cell due to its biodegradability, biochemical compatibility, and having a positive charge in the neutral state (pH=7). Chitosan lactate nanoparticles loaded with siRNA effectively inhibited the Tim-3/STAT3 axis, which was accompanied by suppression of proliferation, colony forming ability, migration and angiogenesis in cancer cells. Also, due to the role of Tim-3 as an immune check point in cellular immunity, we have seen a stronger suppression of cancer cells than STAT3 inhibition alone.