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中国生物工程杂志

China Biotechnology
China Biotechnology
China Biotechnology  2023, Vol. 43 Issue (2/3): 15-25    DOI: 10.13523/j.cb.2207068
    
The Progress of Hydrophobin-based Drug Delivery System
ZHANG Wen-hui**,YAN Jian-yuan**,CHEN Yu-ping***()
Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, School of Pharmacy, University of South China, Hengyang 421001, China
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Abstract  

The strong hydrophobicity, low stability and high side effects of drugs largely limit their clinical use. Drug delivery system (DDS) has undergone fast growth. It can effectively carry and protect drugs, thus increasing their biocompatibility, action specificity and effectiveness. Hydrophobins are small molecular proteins secreted during the special period of fungi, such as the development of fungal fruiting bodies. They possess unique amphiphilicity to aid their self-assembly into micellar structure and modification for other DDSs progress, while their extremely low immunogenicity and cytotoxicity further support their application in drug delivery. This paper reviews the research progress of hydrophobin-based DDS in recent years.

Key words： Drug delivery system      Protein micelles      Hydrophobin      Fungus     
Received: 31 July 2022      Published: 31 March 2023
ZTFLH:  Q819  
Corresponding Authors: ***Yu-ping CHEN     E-mail: yuingc@usc.edu.cn
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Wen-hui ZHANG
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Cite this article:

ZHANG Wen-hui, YAN Jian-yuan, CHEN Yu-ping. The Progress of Hydrophobin-based Drug Delivery System. China Biotechnology, 2023, 43(2/3): 15-25.

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https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2207068     OR     https://manu60.magtech.com.cn/biotech/Y2023/V43/I2/3/15

Fig.1 Self-assembly of hydrophobin at the hydrophilic and hydrophobic interface
类型 疏水蛋白 来源 递药体系 功能 参考文献
I型 HGFI 灰树花 Cur 增强药物抗肿瘤效果 [21]
I型 HGFI 灰树花 Cur 增加药物溶解性和稳定性 [22]
I型 HGFI 灰树花 menaquinone-7 增加药物溶解性 [23]
I型 MGF3、MGF6 灰树花 IND 增加药物的溶解性和稳定性,缓释药物 [24]
I型 MG24 灰树花 MWCNTS 提高纳米管的分散稳定性 [25]
I型 MGF6 灰树花 MGF6-HNTS-Dox 促进药物分散和延缓药物释放 [26]
I型 HPB 真菌 HPB-PLGA-Cur 增强药物抗肿瘤效果 [27]
II型 HFB-1 里氏木霉菌 HFB-1-Nio-DOX 改善药物分布、增加药物血液循环时间和免疫逃逸功能 [28]
II型 HFBIV 里氏木霉菌 Tf-HFBIV-Psi 靶向配体,提高纳米颗粒摄取 [29]
II型 HFBII 里氏木霉菌 HFBII-NP-PTX 谷胱甘肽响应性缓释药物,降低药物IC50 [30]
II型 HFBII 里氏木霉菌 HFBII-FNPs 降低纳米颗粒与血浆蛋白的吸附性 [31]
II型 HFBII 里氏木霉菌 HFBII-NFC-O-IBU 作为表面活性剂稳定乳液 [32]
II型 HFBI 里氏木霉菌 FA 结晶抑制剂 [33]
Table 1 Hydrophobins-based drug delivery systems
用途分类 融合疏水蛋白 表达体系 纯化方法 优点 应用 文献
抗原抗体的制备、检测和固定 rK39-HFBI 植物 ATPS 消除了通过额外步骤去除纯化标签的需要 用于内脏利什曼病免疫诊断 [35]
Hydrophobin-Protein A 植物 单一ATPS 纯化成本更低并且蛋白质回收率相当,增加蛋白A树脂的寿命,减少单克隆抗体的损失 提高西尼罗河病毒单克隆抗体(E16)产量 [36]
HFB-DomIII-1
HFB-DomIII-2		 昆虫幼虫杆状病毒系统 ATPS 快速、简便和成本效益高的方法用于生产与HFB融合的重组抗原,并且重组抗原的安全性较高 固定抗原DENV,检测抗体水平 [38]
医疗器械抗菌涂层 LL37-Vmh2 大肠杆菌表达系统 超滤回收
Vmh2		 提高抗菌肽抗表皮葡萄球菌生物膜活性并且对革兰氏阳性和革兰氏阴性菌都有效 用于医疗器械的涂层,抑制其表面微生物生长 [40]
生物传感器 ArsC-Vmh2 Vmh2-ArsC 大肠杆菌表达系统 包涵体变性复性 嵌合蛋白既具有vm2的黏附特性,又具有耐热砷酸还原酶的砷传感能力 电化学生物传感器用于检测As(III) [41]
Ccg2-EPSPS 大肠杆菌表达系统 镍柱亲和
纯化		 降低了传统传感器程序的复杂性,并允许实时检测 高度灵敏传感器用于检测草甘膦 [42]
Lac-Vmh2 毕赤酵母表达系统 上清液浓缩并透析 方法简单、环保且用途广泛,既可用作FLG的表面活性剂,也克服了在剥离石墨烯过程中的分散稳定性 用于修饰玻碳类化合物的电化学传感器 [43]
Vmh2-ScFvSTX
Vmh2-ScFvDA		 大肠杆菌表达系统 包涵体变性复性 方法简单智能,Vmh2允许ScFv将MBs直接功能化不需任何化学修饰,MBs可以使用磁场回收重复利用 固定抗体ScFvs,诊断抗原 [34]
Table 2 New biomedical hydrophobin-fused proteins
融合标签 蛋白质 表达体系 纯化方法 优点 应用 文献
ramp DewA 大肠杆菌表达系统 异丙醇改进的双相水分离 避免耗时且低效的蛋白质复性和纯化步骤,且纯化过程只使用IPA一种试剂 提高疏水蛋白的表达和产量 [45]
CBD CBD-HGFI 大肠杆菌表达系统 镍柱亲和纯化 CBD特异性与BC结合,促进从粗提取物中快速分离和纯化疏水蛋白 提高疏水蛋白的表达和产量 [44]
Ffu312 EAS-Ffu312
HFBII-Ffu312		 大肠杆菌表达系统 镍柱亲和纯化 融合蛋白分泌到周质和培养基中简化了纯化,便于提供氧化环境和二硫异构酶,促进疏水蛋白二硫键的形成 提高疏水蛋白的表达和产量 [47]
Table 3 Fusion tags for the preparation of biomedical hydrophobins
表达体系 疏水蛋白 纯化方法 优点 应用 文献
大肠杆菌无细胞表达系统 I型:EASΔ15、EAS、DewY - a DewA mutant、RodA、MPG1
II型:NC2		 Ni-NTA亲和层析 克服重组疏水蛋白的变性重折叠问题以允许正确折叠并提高蛋白质产量,反应环境可以直接控制 提高疏水蛋白的表达和产量 [49-50]
SHuffle T7大肠
杆菌表达系统		 I型:PC1、WL1、SL1、SC16 IMAC柱纯化 有效形成二硫键的还原环境,持续产生高水平、高纯度的疏水蛋白 提高疏水蛋白的表达和产量 [51]
Table 4 New expression system for biomedical hydrophobins
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