مشخصات پژوهش

Despite current treatments such as chemotherapy, many people around the world still die from breast cancer disease every year, which is mainly due to drug resistance in breast tumor cells and tumor recurrence. Also, the side effects caused by chemotherapy drugs are sometimes very severe, and it is necessary to reduce the required dose of these drugs with different methods. Interleukin 6 (IL-6) is one of the molecules that play a significant role in the development of breast cancer and drug resistance in breast tumor cells, and its inhibition can help in the treatment of this malignancy. Doxorubicin (DOX) is one of the common chemotherapy drugs that prevents tumor progression by interfering with DNA replication and transcription. In the present study, chitosan lactate (CL) nanoparticles were used for simultaneous delivery of DOX and anti-IL-6 siRNA molecules to 4T1 mouse breast cancer cells. Nanocarriers protect the drug from degradation and increase its half- life in the bloodstream and increase the solubility of hydrophobic drugs. Also, by specifically targeting the tumor, these carriers increase the drug concentration at the tumor site and reduce the toxicity of the drugs for other normal cells of the body. CL nanoparticles were synthesized by "ionic gelation" method. After evaluating the characteristics, the CL nanoparticles and CL+DOX, CL+siRNA and CL+DOX+siRNA formulations, as well as free DOX, were transferred to cultured 4T1 cells. Then, their effects on this cell line were investigated. Among these evaluations, MTT, CAM, scratch test, colony formation test, evaluation of related gene expression and measurement of interleukin-6 protein levels can be mentioned. The results showed that CL + DOX + siRNA nanoparticles have the highest toxicity and inhibitory effect on 4T1 cancer cells, compared to when each of the nanoparticles containing siRNA and DOX and DOX were applied separately. Also, the combined treatment significantly reduced the angiogenesis rate and th