Combination Of Oxaliplatin/Esveratrol Nanoparticles In The Treatment Of Colorectal Cancer

In this study,carboxymethyl chitosan(CMCS)was selected as the carrier.Oxaliplatin nanoparticles(CMCS-OXE NPs)and resveratrol nanoparticles(CMCS-Res NPs)were successfully prepared with the oxaliplatin(OXE)and resveratrol(Res)used as model drugs.A series of physical and chemical properties of nanoparticles were characterized.At the same time,we explored the drug release properties of nanoparticles in vitro and the stability of nanoparticles.And the anti-colon cancer activities in vivo and in vitro were evaluated.The main research contents and conclusions are as follows:CMCS-OXE NPs nanoparticles and CMCS-Res NPs nanoparticles were prepared by ion crosslinking and emulsification crosslinking,respectively.The encapsulation efficiency and drug loading of nanoparticles were determined by HPLC.The encapsulation efficiency and drug loading of CMCS-OXE NPs were 60% and 11%,respectively.The encapsulation efficiency and drug loading of CMCS-Res NPs was 65% and 10%,respectively.The average particle size and zeta potential were measured by dynamic light scattering method: CMCS-OXE NPs(190 nm ± 1)and CMCS-Res NPs(162 nm ± 1).The morphology of nanoparticles was round or quasi-circular by transmission electron microscopy(TEM).The release of nanoparticles in vitro was measured by dynamic dialysis method.The results showed that nanoparticles had obvious sustained release effect.The cytotoxicity of nanoparticles and polymer CMCS to SW480 cells and CT26 cells(both cancer cells)was detected by CCK-8 assay.The results indicate that the non-toxicity of CMCS at any concentration of study,which confirmed its good biocompatibility.Both free-drugs and nanoparticles inhibited the proliferation of cancer cells in varying degrees in a dose-dependent and time-dependent manner.Compared with the free-drugs and the single nanoparticles,the combined nanoparticles showed more significant anti-colon cancer activity.An animal model of colon cancer was established by inoculating CT26 cells subcutaneously into BALB/c mice.The toxic and side effects of anti-cancer drugs on tumor-bearing mice were investigated by H&E staining and serum factor detection(Alanine aminotransferase(ALT)?aspartate aminotransferase(AST)?Urea and creatinine(Cr)).The results showed that the toxic and side effects of(liver,spleen,lung,brain)organs of oxaliplatin and resveratrol were not obvious in the dose of this experiment.The anti-colon cancer activity and its mechanism of the nanoparticles were investigated by the curve of tumor size and body weight in mice?fluorescence staining and TUNEL method.It was found that the combined nano-drug showed stronger anti-colon cancer activity than the free drugs,which was consistent with the results of cell activity in vitro.In addition,the mechanism of Oxaliplatin combined with resveratrol in the treatment of colon cancer was studied by investigating the changes of the proportion of MDSCs cells and the expression of ?-SMA and CUGBP1 proteins in tumor tissues.