Wei Yamin, Li Yulin, Zhang Heng, Zhang Yiqing, Wang Xiaojun, Wang Huirui, Xiao Pengli, Qian Peng, Ren Lei, Wang Yunlong
School of Life Sciences, Zhengzhou University, Zhengzhou 450006, Henan, China.
Henan Bioengineering Technology Research Center, Zhengzhou 450000, Henan, China.
Sheng Wu Gong Cheng Xue Bao. 2022 Mar 25;38(3):1039-1049. doi: 10.13345/j.cjb.210252.
Hepatitis B virus core protein (HBc) has become a hot spot in drug carrier protein research due to its natural particle self-assembly ability and ease of modification. The truncation of the C-terminal polyarginine domain (CTD, aa 151-183) of HBc does not affect the self-assembly of the particles. However, it does affect the internal and external charges of the particles, which may subsequently affect drug encapsulation. Thus, the truncated C-terminal polyarginine domain (CTD) of HBc and the inserted RGD peptide were selected to construct and express three HBc variants (RH) encapsulated with ICG (RH/ICG) with different C-terminal lengths to compare the stability and drug activity of their nanoformulations. RH160/ICG was found to have a great advantages in encapsulation efficiency and biological imaging. Compared with other HBc variants, RH160/ICG significantly improved encapsulation efficiency, up to 32.77%±1.23%. Cytotoxicity and hemolysis assays further demonstrated the good biocompatibility of RH160/ICG. Cell uptake and imaging experiments in mice showed that RH160/ICG could efficiently deliver ICG in tumor cells and tumor sites with good imaging effect. This research provides a new direction for further expanding the diagnosis and treatment application of ICG and development of HBc-based nanoparticle drug carrier platform.
乙肝病毒核心蛋白（HBc）因其天然的颗粒自组装能力和易于修饰的特点，已成为药物载体蛋白研究的热点。HBc C末端多聚精氨酸结构域（CTD，氨基酸151 - 183）的截短不影响颗粒的自组装。然而，它确实会影响颗粒的内外电荷，这可能随后影响药物包封。因此，选择截短的HBc C末端多聚精氨酸结构域（CTD）和插入的RGD肽来构建并表达三种不同C末端长度且包载吲哚菁绿（ICG）的HBc变体（RH），即RH/ICG，以比较它们纳米制剂的稳定性和药物活性。发现RH160/ICG在包封效率和生物成像方面具有很大优势。与其他HBc变体相比，RH160/ICG显著提高了包封效率，高达32.77%±1.23%。细胞毒性和溶血试验进一步证明了RH160/ICG具有良好的生物相容性。小鼠体内的细胞摄取和成像实验表明，RH160/ICG能够在肿瘤细胞和肿瘤部位高效递送ICG，成像效果良好。该研究为进一步拓展ICG的诊断和治疗应用以及基于HBc的纳米颗粒药物载体平台的开发提供了新方向。
