Zhang Liqiao, Pan Xiuhua, Xu Lixing, Zhang Linlin, Huang Haiqin
Department of Pharmacy, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China Chengdu 611731 PR China.
Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University Nanjing 210009 China.
RSC Adv. 2021 Jan 28;11(10):5348-5360. doi: 10.1039/d0ra09589c.
Liver fibrosis, originating from activated hepatic stellate cells (HSCs), is receiving much attention in the treatment of clinical liver disease. In this study, mitochondria-targeted curcumin (Cur) loaded 3-carboxypropyl-triphenylphosphonium bromide-poly(ethylene glycol)-poly(ε-caprolactone) (CTPP-PEG-PCL) micelles were constructed to prolong the systemic circulation of Cur, improve the bioavailability of Cur and play a precise role in anti-fibrosis. The prepared Cur-CTPP-PEG-PCL micelles with a spherical shape had satisfactory dispersion, low critical micelle concentration (CMC) and high encapsulation efficiency (92.88%). The CTPP modification endowed good endosomal escape ability to the CTPP-PEG-PCL micelles, and micelles could be selectively accumulated in mitochondria, thereby inducing the enhanced cell proliferation inhibition of HSC-T6 cells. Mitochondrial Membrane Potential (MMP) was greatly reduced due to the mitochondrial-targeting of Cur. Moreover, the system circulation of Cur was extended and bioavailability was significantly enhanced . As expected, Cur loaded CTPP-PEG-PCL micelles were more effective in improving liver fibrosis compared with Cur and Cur-mPEG-PCL micelles. In conclusion, the Cur-CTPP-PEG-PCL based micelles can be a potential candidate for liver fibrosis treatment in future clinical applications.
肝纤维化起源于活化的肝星状细胞（HSCs），在临床肝病治疗中备受关注。在本研究中，构建了负载线粒体靶向姜黄素（Cur）的3-羧丙基三苯基溴化鏻-聚（乙二醇）-聚（ε-己内酯）（CTPP-PEG-PCL）胶束，以延长Cur的全身循环时间，提高Cur的生物利用度，并在抗纤维化中发挥精准作用。所制备的呈球形的Cur-CTPP-PEG-PCL胶束具有良好的分散性、低临界胶束浓度（CMC）和高包封率（92.88%）。CTPP修饰赋予CTPP-PEG-PCL胶束良好的内体逃逸能力，且胶束可选择性地在线粒体中积累，从而诱导对HSC-T6细胞增强的细胞增殖抑制作用。由于Cur的线粒体靶向作用，线粒体膜电位（MMP）大大降低。此外，Cur的系统循环时间得以延长，生物利用度显著提高。正如预期的那样，与Cur和Cur-mPEG-PCL胶束相比，负载Cur的CTPP-PEG-PCL胶束在改善肝纤维化方面更有效。总之，基于Cur-CTPP-PEG-PCL的胶束可能成为未来临床应用中治疗肝纤维化的潜在候选药物。
