Title | Activity and Tissue Distribution of Antisense Oligonucleotide CT102 Encapsulated with Cytidinyl/Cationic Lipid against Hepatocellular Carcinoma |
Authors | Guan, Jing Pan, Yufei Li, Huantong Zhu, Yuejie Gao, Yujing Wang, Jie Zhou, Ying Guan, Zhu Yang, Zhenjun |
Affiliation | Guizhou Univ, Inst Agrobioengn, Coll Life Sci,Minist Educ, Key Lab Plant Resource Conservat & Germplasm Inno, Guiyang 550025, Peoples R China Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China Guizhou Univ Tradit Chinese Med, Coll Pharmaceut Sci, Guian New Area 550025, Peoples R China |
Keywords | SORAFENIB RESISTANCE IN-VITRO GROWTH MECHANISMS TARGETS SIRNA |
Issue Date | May-2022 |
Publisher | MOLECULAR PHARMACEUTICS |
Abstract | Insulin-like growth factor 1 receptor (IGF1R), a cell surface receptor with tyrosine kinase (TK) activity, has ligands abnormally expressed in acute leukemia, multiple myeloma, breast, prostate, cervical, and nonsmall cell lung cancers, Ewing's sarcoma, and other malignant tumors. IGF1R mediates the malignant proliferation, invasion, and metastasis of tumor cells through a variety of signal transduction pathways, and it is also involved in tumor angiogenesis and tumor cell antiapoptosis. In this study, the neutral cytidinyl lipid DNCA and cystine skeleton cationic lipid CLD from our laboratory could be optimized to encapsulate antisense oligonucleotide (ASO) CT102 to form stable and uniform Mix/CT102 nanoparticles (NPs), which could specifically target tumor cells that highly expressed IGF1R in viro by intravenous administration. Compared with naked CT102, the lipid complex could promote the uptake and late apoptosis levels of HepG2 and Huh-7 cells, inhibiting cell proliferation efficiently. We also found that Mix/CT102 could enter nucleus in about 2 h, effectively downregulating the mRNA level of IGF1R. The in vivo efficacy experiment demonstrated that in the group that received the optimal dose of Mix/CT102, tumor volume was reduced 8-fold compared with the naked dose group. Meanwhile, in vivo distribution studies showed that the nanoparticles had a predominant accumulation capacity in liver tissue. These results indicated that clinicians can expect the Mix/CT102 nanocomposite to be very effective in reducing the dose and frequency of clinically administered CT102, thereby reducing the side effects of ASOs. |
URI | http://hdl.handle.net/20.500.11897/648829 |
ISSN | 1543-8384 |
DOI | 10.1021/acs.molpharmaceut.2c00026 |
Indexed | SCI(E) |
Appears in Collections: | 药学院 天然药物与仿生药物国家重点实验室 |