PREPARATION AND CHARACTERIZATION OF TUMOR CELL LYSATE AND POLY-IC LOADED POLY ( LACTIC-CO-GLYCOLIC ACID) NANOPARTICLES AND EVALUATION OF THEIR ANTI-TUMOR EFFECTS IN MOUSE MODEL OF BREAST CANCER

Cancer immunotherapy, despite its many benefits, faces major challenges. Nanoparticles are drug delivery systems that may address these challenges. The goal of this study was to produce the tumor cell lysate and Poly-IC loaded nanoparticles with desirable properties and evaluation of their therapeutic effects in mouse model of breast cancer. Nanoparticles were prepared by the double emulsion solvent-evaporation method, using poly (vinyl alcohol) (PVA) as a surfactant. Effects of molecular weight variation and the degree of hydrolyzation of PVA were investigated for the particle size, polydispersity index, encapsulation efficiency and the residual surfactant percentage of nanoparticles. 4T1 Cell line was used to induce the breast tumor in mice. To evaluate the effectiveness of the vaccine, tumor growth rate, proliferation of splenic cells by MTT assay and Delayed Type Hypersensitivity (DTH) reaction were evaluated. These results showed that the use of polyvinyl alcohol with a molecular weight of 13-23 kDa and 87-89% hydrolysis, produced nanoparticles with desirable properties. Although injection of nanoparticles containing tumor cell lysate with or without poly-IC to mice, caused a significant decrease in tumor growth, increased splenic lymphocyte proliferation, and delayed type hypersensitivity response in these two groups. But these changes, in the group that received nanoparticles containing the tumor cell lysate with Poly-IC were more significant than other groups. The results showed that the co-encapsulation of tumor cell lysate and poly-IC in one nanoparticle, due to the effects of Poly-IC on the maturation and activation of dendritic cells, enhance anti-tumor immune responses and can be considered as an effective therapeutic strategy for the treatment of breast cancer.