Investigation on efficacy against hepatocellular carcinoma of novel antisense oligonucleotide targeting IGF1R mRNA encapsulated with neutral cytidinyl/cationic lipid in vitro
10.16438/j.0513-4870.2023-1285
- VernacularTitle:靶向IGF1R mRNA的反义寡核苷酸修饰物新型制剂体外抗肝癌活性研究
- Author:
Yang PU
1
;
Jing GUAN
2
;
Qian-yi HE
3
;
Yue-jie ZHU
3
;
De-lin PAN
1
;
Zhu GUAN
3
;
Zhen-jun YANG
2
Author Information
1. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
2. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
3. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
- Publication Type:Research Article
- Keywords:
antisense oligonucleotide;
neutral cytidine lipid;
cystine backbone cationic lipid;
insulin-like growth factor 1 receptor;
hepatocellular carcinoma
- From:
Acta Pharmaceutica Sinica
2024;59(5):1441-1448
- CountryChina
- Language:Chinese
-
Abstract:
Antisense oligonucleotides are a type of gene therapy that targets mRNA and inhibits gene expression. They have been applied in the treatment of various diseases, but there are still problems with poor enzyme stability and high dosage in vivo, due to the shortage of appropriate delivery system. Insulin-like growth factor 1 receptor (IGF1R) is a cell surface receptor with tyrosine kinase activity. Its expression is abnormal in a variety of malignant tumors. It mediates the malignant proliferation, migration and invasion of tumor cells through a variety of ways. In this study, an antisense oligonucleotide (ASO, N04) targeting IGF1R mRNA was designed and chemically modified (PS, 2'-OMOE), then neutral cytidine lipid DNCA and cystine backbone cationic lipid CLD (Mix) were used to encapsulate ASOs. The particle size, polymer dispersity index and ζ potential of the formulations were 151 nm, 0.18 and -3.9 mV. The nanoparticles entered liver cancer cells (HepG-2, Huh-7), silenced target mRNA, arrested cell cycle in S phase, promoted apoptosis, and inhibited the proliferation efficiently. These results indicate that Mix/N04MOE5 has great potential in tumor treatment, which provides a basis for further research on novel agents against hepatocellular carcinoma.
