噻吩衍生物作为新型抗癌药物及其利用叶酸受体靶向纳米载体的治疗递送

Thiophene Derivatives as New Anticancer Agents and Their Therapeutic Delivery Using Folate Receptor-Targeting Nanocarriers.

作者信息

Zhao Menghui, Cui Yaxin, Zhao Lang, Zhu Tianyu, Lee Robert J, Liao Weiwei, Sun Fengying, Li Youxin, Teng Lesheng

机构信息

School of Life Sciences and College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China.

College of Pharmacy, The Ohio State University, 500 W 12th Avenue, Columbus 43210, United States.

出版信息

ACS Omega. 2019 May 22;4(5):8874-8880. doi: 10.1021/acsomega.9b00554. eCollection 2019 May 31.

A series of thiophene derivatives were synthesized by functionalization of 2,3-fused thiophene scaffolds. Their cytotoxicity was assessed against HeLa and Hep G2 cells. Compound 480 was identified as a promising candidate because of its low IC in HeLa (12.61 μg/mL) and Hep G2 (33.42 μg/mL) cells. The drug was loaded into folic acid (FA)-coated nanoparticles (NPs) to address its poor water solubility and to improve its selectivity for cancer cells. Compound 480 was shown to induce apoptosis by changes in mitochondrial membrane potential (ΔΨ) and the reactive oxygen species level. Furthermore, FA-modified NPs enhanced uptake capacity compared to unmodified controls by flow cytometry. This drug delivered in folate nanocarriers is promising for the treatment of cancers.

通过对2,3-稠合噻吩骨架进行功能化反应，合成了一系列噻吩衍生物。评估了它们对HeLa细胞和Hep G2细胞的细胞毒性。化合物480因其在HeLa细胞（12.61 μg/mL）和Hep G2细胞（33.42 μg/mL）中的低半数抑制浓度（IC）而被确定为有前景的候选物。将该药物负载到叶酸（FA）包被的纳米颗粒（NP）中，以解决其水溶性差的问题，并提高其对癌细胞的选择性。化合物通过线粒体膜电位（ΔΨ）和活性氧水平的变化诱导细胞凋亡。此外，通过流式细胞术检测，与未修饰的对照相比，FA修饰的NP增强了摄取能力。这种负载于叶酸纳米载体中的药物在癌症治疗方面具有前景。