School of Life Sciences, Zhengzhou University, Zhengzhou 450006, Henan, China;Henan Bioengineering Technology Research Center, Zhengzhou 450000, Henan, China;Zhengzhou Technical College, Zhengzhou 450052, Henan, China 在期刊界中查找 在百度中查找 在本站中查找
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摘要:
乙肝病毒核心蛋白(hepatitis B virus core protein,HBc)由于其天然的颗粒自组装能力和易修饰性,已然成为药物载体蛋白研究的热点。HBc的C-末端聚精氨酸结构域(CTD,aa 151–183)的截短与否不会影响颗粒的自组装特性,但对颗粒的内外电荷会产生一定影响,进而影响药物包封。基于此,本研究选择截短HBc的CTD和插入RGD肽,构建并表达3种不同C末端长度的HBc变体(RH)包封ICG (RH/ICG),比较其纳米制剂的稳定性和药物活性。研究发现RH160/ICG在包封效率和生物成像方面存在较大优势。相比于其他HBc蛋白变体,RH160/ICG可明显提高包封效率,最高可达32.77%±1.23%。细胞毒性和溶血实验进一步表明RH160/ICG具有良好的生物相容性。细胞摄取和小鼠体内成像实验均显示RH160/ICG可在4T1小鼠乳腺癌细胞和肿瘤部位中高效递送ICG,具有较好的成像效果。研究结果为进一步扩大ICG的诊疗应用和开发以HBc为基础的纳米颗粒药物载体平台提供新的方向。
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 in vivo 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.
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