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Investigation on efficacy against hepatocellular carcinoma of novel antisense oligonucleotide targeting IGF1R mRNA encapsulated with neutral cytidinyl/cationic lipid in vitro
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Yang PU1, Jing GUAN2, 3, Qian-yi HE2, Yue-jie ZHU2, De-lin PAN1, *, Zhu GUAN2, Zhen-jun YANG2, 3, *
Acta Pharmaceutica Sinica | 2024, 59(5) : 1441 - 1448
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Acta Pharmaceutica Sinica | 2024, 59(5): 1441-1448
• Original Articles •
Investigation on efficacy against hepatocellular carcinoma of novel antisense oligonucleotide targeting IGF1R mRNA encapsulated with neutral cytidinyl/cationic lipid in vitro
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Yang PU1, Jing GUAN2, 3, Qian-yi HE2, Yue-jie ZHU2, De-lin PAN1, *, Zhu GUAN2, Zhen-jun YANG2, 3, *
Affiliations
  • 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
  • 3. College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
Published: 2024-05-12 doi: 10.16438/j.0513-4870.2023-1285
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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.

antisense oligonucleotide  /  neutral cytidine lipid  /  cystine backbone cationic lipid  /  insulin-like growth factor 1 receptor  /  hepatocellular carcinoma
Yang PU, Jing GUAN, Qian-yi HE, Yue-jie ZHU, De-lin PAN, Zhu GUAN, Zhen-jun YANG. Investigation on efficacy against hepatocellular carcinoma of novel antisense oligonucleotide targeting IGF1R mRNA encapsulated with neutral cytidinyl/cationic lipid in vitro[J]. Acta Pharmaceutica Sinica, 2024 , 59 (5) : 1441 -1448 . DOI: 10.16438/j.0513-4870.2023-1285
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Year 2024 volume 59 Issue 5
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Article Info
doi: 10.16438/j.0513-4870.2023-1285
  • Receive Date：2023-11-14
  • Online Date：2025-11-27
  • Published：2024-05-12
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History
  • Received：2023-11-14
  • Revised：2024-04-07
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Affiliations
    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
    3. College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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