The Preparation And Study Of An Anti-tumor Nano-drug For Reversion Drug Resistance And Inhibition Migration Of Colorectal Cancer

Colorectal cancer(CRC),also known as colorectal cancer,is one of the high-incidence malignant tumors in the world,and its incidence rate is the third highest in the world,accounting for 9.4% of all cancer deaths,and it is the second leading cause of cancer death.The pathogenesis of colorectal cancer involves many factors,such as heredity,environment,diet and intestinal flora.Among them,intestinal flora plays an important role in the occurrence and development of digestive system malignant tumors,especially Fusobacterium nucleatum(Fn).Fn is a kind of Gram-negative anaerobic bacteria,which normally parasitizes the oral cavity and is a conditional pathogen.Studies have shown that Fn causes chemotherapy resistance in colorectal cancer through autophagy,and the abundance of Fn is directly related to the occurrence,development and metastasis of colorectal cancer.It was further found that Fn promoted the invasion of colorectal cancer cells by activating the NF-κB signaling pathway of host cells,thus promoting the metastasis of CRC.Therefore,in view of the problem that Fn in intestinal microflora is easy to lead to the proliferation and migration of colorectal cancer,lauric acid(LA),which can kill Fn,is used to regulate the tumor microflora,inhibit the proliferation and migration of tumor cells,reverse the drug resistance of colorectal cancer cells to chemotherapy drugs,enhance the chemotherapy effect,and help to achieve better anti-tumor efficacy.Based on this,we selected hyperbranched polyglycidyl ether(PG)which is easy to synthesize as the carrier,and grafted LA and platinum(IV)prodrug(Ox Pt-COOH)onto PG to obtain PG-Pt-LA,and then supermolecularly assembled it with cucurbit [7]urea(CB[7])to obtain the nano-drug PG-PT-LA/CB [ Under the competition of over-expressed spermine in tumor microenvironment,PG-Pt-LA/CB[7] was disassembled,so that antibacterial and anticancer drugs were exposed/released.In vitro cell experiments showed that the cell survival rate of nanoparticles was 34%even in the presence of Fn.At the same time,migration and invasion experiments showed that CT26 cells were obviously inhibited after drug treatment,and in vivo experiments showed that PG-Pt-LA/CB[7].