Meng Zhengjie, Yang Xiaoyan, Hu Die, Wang Kaikai, Zhi Feng, Chen Xi, Gong Guangming, Wu Jinhui, Hu Yiqiao
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, People's Republic of China; College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, 211816, People's Republic of China.
J Pharm Sci. 2015 Mar;104(3):1045-55. doi: 10.1002/jps.24290. Epub 2015 Jan 14.
Protein-based nanoparticles hold great promises in both preclinical and clinical practices, such as oncology diagnosis and treatment, because of their high biocompatibility and biodegradability. However, the complicated preparation and lack of targeting specific cells or tissues may limit their further uses. To overcome these limitations, we developed a novel replacing method for preparing dual-functional protein nanocarrier, such that one function is capable of encapsulating small molecule into protein, whereas the other function is cable of recognizing CD163 receptor [hemoglobin (Hb) scavenger receptor]. In this study, Hb was chosen as the targeting drug carrier. First, the heme group in the Hb was removed and replaced by paclitaxel (PTX) to form nanoparticles (Gb-NPs-PTX). The resulted Gb-NPs-PTX showed spherical shape and their diameter could be controlled in the range of 120-160 nm by altering the ratio of PTX to Hb. The binding activity of Gb-NPs-PTX to CD163 was confirmed by cell uptake in CD163(+) Chinese hamster ovary cells. Results in vivo also showed a CD163-dependent tissue accumulation of Gb-NPs-PTX in mice. In summary, by using the novel replacing method, PTX could be easily encapsulated into Hb nanoparticles and the targeting effects of Hb could also be kept.
基于蛋白质的纳米颗粒因其高生物相容性和可生物降解性，在临床前和临床实践（如肿瘤学诊断和治疗）中具有巨大潜力。然而，其复杂的制备过程以及缺乏对特定细胞或组织的靶向性，可能会限制它们的进一步应用。为克服这些限制，我们开发了一种制备双功能蛋白质纳米载体的新型替代方法，其中一种功能能够将小分子包裹进蛋白质中，而另一种功能能够识别CD163受体[血红蛋白（Hb）清除受体]。在本研究中，选择Hb作为靶向药物载体。首先，去除Hb中的血红素基团并用紫杉醇（PTX）取代，以形成纳米颗粒（Gb-NPs-PTX）。所得的Gb-NPs-PTX呈球形，通过改变PTX与Hb的比例，其直径可控制在120 - 160 nm范围内。通过CD163(+)中国仓鼠卵巢细胞的细胞摄取，证实了Gb-NPs-PTX与CD163的结合活性。体内实验结果还表明，Gb-NPs-PTX在小鼠体内呈现出依赖CD163的组织蓄积。总之，通过使用这种新型替代方法，PTX能够轻松地包裹进Hb纳米颗粒中，同时还能保留Hb的靶向作用。
