Yang Pu, Quanxin Wang, Yufei Pan, Xixian Wang, Zhu Guan, Yuejie Zhu, Zhenjun Yang
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引用次数: 0
Abstract
Hepatocellular carcinoma (HCC) is the most prevalent form of invasive liver cancer, representing over 90% of all liver cancer cases. Currently, there is a lack of targeted therapy for HCC. Insulin-like growth factor 1 receptor (IGF1R) is abnormally expressed in HCC, leading to the malignant proliferation and contributing to the antiapoptosis mechanisms in tumor cells. In this study, small interfering RNAs targeting IGF1R mRNA (siIGF1Rs) have been designed. Additionally, a full 2'-F/2'-OMe modification with partial phosphorothioation was applied to improve the biological properties of these siIGF1Rs. Based on previous research, stable lipid complexes with uniform particle sizes were constructed using cytidinyl lipid DNCA/cationic lipid CLD (Mix) supplemented with DSPE-PEG (siIGF1R/Mix/PEG). The complexes were formed through hydrogen-bonding, π-π stacking, and electrostatic interactions. The siIGF1R/Mix/PEG complex entered the cytoplasm and nucleus of HCC cells, reduced IGF1R mRNA and pre-mRNA levels by over 95% and 50% respectively, further arrested the cell cycle in the S phase, and promoted cell apoptosis. Importantly, siIGF1R/Mix/PEG (0.8 mg/kg, i.v.) selectively accumulated in the tumor, significantly inhibiting tumor growth by 91.31% compared to the naked siRNA group, with slower release and a more prolonged effect.
期刊介绍:
Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development.
Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.