Long-acting anti-colorectal cancer by nanocomplex co-regulating Bmi1 through miR-218 and siCCAT1

Nucleic acid drug has many advantages in tumor treatment, but the characteristic of difficult delivery limits the development of this therapy. In this study, we used 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(poly-ethylene glycol)2000 (DSPE-PEG) modified with glucose (DSPE-PEG-Glucose) and polyethyleneimine-poly (d, L-lactide) (PEI-PDLLA) to construct small interfering RNA CCAT1 (siCCAT1) and microRNA-218 (miR-218) co-delivery nanocomplex with glucose transporter type 1 (Glut1) targeting effects (GDCMNP). GDCMNP could be rapidly enriched at the tumor site and sequentially release two types of RNAs. The anti-tumor effect of GDCMNP was mainly due to the co-regulation of the proto-oncogene B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi1) and epithelial-mesenchymal transition (EMT) by siCCAT1 and miR-218, which improved apoptosis and reduced the ability to migrate and invade. It was worth mentioning that GDCMNP played a long-term effect against colorectal cancer (CRC) in both subcutaneous and orthotopic CRC tumor models. In summary, we constructed a promising approach for the treatment of CRC by nucleic acids.