Long-acting anti-colorectal cancer by nanocomplex co-regulating Bmi1 through miR-218 and siCCAT1
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY(2023)
摘要
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.
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关键词
Nucleic acid therapy,Nanocomplex,Dual RNAs,Bmi1,CCAT1,miR-218
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