Tumor Microenvironment-Responsive Lipid Nanoparticle for Blocking Mitosis and Reducing Drug Resistance in NSCLC

IF 6.8 1区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Medicinal Chemistry Pub Date : 2025-01-24 DOI:10.1021/acs.jmedchem.4c02960

Fengrui Yang, Xiao-Rou Jiang, Lingling Lei, Jing-Hao Fu, Zeng-Ping Chen, Ru-Qin Yu

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引用次数: 0

Abstract

Blocking mitosis is a promising strategy to induce tumor cell death. However, AMPK- and PFKFB3-mediated glycolysis can maintain ATP supply and help tumor cells overcome antimitotic drugs. Inhibiting glycolysis provides an opportunity to decrease the resistance of tumor cells to antimitotic drugs. Meanwhile, increased glutathione (GSH) expression in cancer cells due to glycolysis becomes a target for developing microenvironment-responsive drugs. Herein, a novel cationic lipid with disulfide bonds in hydrophobic tails was synthesized and used to prepare a GSH-triggered lipid nanoparticle named 2-DG@SLNP(siR) encapsulating both Plk1 siRNA and 2-deoxyglucose (2-DG) for blocking mitosis and reducing drug resistance of nonsmall cell lung cancer (NSCLC) cells in vivo. Experimental results showed that the NSCLC cell cycle was arrested at the G2/M phase by Plk1 siRNA and glycolysis was effectively inhibited by 2-DG, demonstrating the potential of 2-DG@SLNP(siR) as an efficient platform for blocking mitosis and reducing drug resistance of cancer cells.

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来源期刊

Journal of Medicinal Chemistry 医学-医药化学

CiteScore

4.00

自引率

11.00%

发文量

804

审稿时长

1.9 months

期刊介绍： The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents. The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.