EpCAM Aptamer-Functionalized Cationic Liposome-Based Nanoparticles Loaded With Mir-139-5p For Targeted Therapy In Colorectal Cancer

Colorectal cancer(CRC)is one of the most common cancers worldwide,and about 700,000 people die from CRC each year.About 50%of patients display regional or distant metastases at the time of diagnosis.The 5-year survival rate following distant metastatic diagnosis is below 10%.At present,the treatment of CRC is mainly performed by surgery,chemotherapy,radiotherapy and targeted therapy.MicroRNA(miRNA)play a vital role in a variety of biological processes.As a therapeutic method,miRNA’s main challenges are rapid degradation,short half-life and off-target effects.Among them,miR-139-5p has been identified as a tumor suppressor gene that is overexpressed in CRC,which helps inhibit the progression of cancer.In this subject,we developed a nanoparticle drug delivery system based on cationic Liposomes.The drug delivery system is loaded with miR-139-5p(miR-139-5p-HSPC/DOTAP/Chol/DSPE-PEG2000-COOH nanoparticles,MNPs)and surface-decorated with epithelial cell adhesion molecule(EpCAM)aptamer(Apt)(miR-139-5p-EpCAM Apt-HSPC/DOTAP/Chol/DSPE-PEG2000-COOH nanoparticles,MANPs)for the targeted treatment of CRC.The size of MANPs is 150.3 ± 8.8 nm and the surface potential is 37.8±3.2 mV.It has a round appearance and negligible hemolysis.MANPs significantly inhibited the proliferation,migration and invasion of HCT116 and HCT8 cells in vitro,and had targeting capabilities for EpCAM(+)cells.NOTCH1 is one of the target genes of miR-139-5p,and it is a cancer-promoting gene for colorectal cancer.Our results showed that MANPs significantly down-regulated the mRNA and protein levels of NOTCH1 in HCT116 and HCT8 cells.In addition,ANPs had significant EpCAM(+)tumor targeting in vivo.MANPs significantly inhibited the development of colorectal cancer in both the subcutaneous tumor model and the peritoneal tumor model.MANPs had no toxic side effects on the main organs of nude mice.Our results demonstrated that MANPs was an effective drug delivery system to deliver therapeutic miR-139-5p to CRC tumor.