合成生物学 ›› 2022, Vol. 3 ›› Issue (2): 279-301.DOI: 10.12211/2096-8280.2022-008
郑涵奇1, 吴晴1, 李洪军1,2, 顾臻1,2,3,4
收稿日期:
2022-01-27
修回日期:
2022-02-21
出版日期:
2022-04-30
发布日期:
2022-05-11
通讯作者:
李洪军,顾臻
作者简介:
基金资助:
Hanqi ZHENG1, Qing WU1, Hongjun LI1,2, Zhen GU1,2,3,4
Received:
2022-01-27
Revised:
2022-02-21
Online:
2022-04-30
Published:
2022-05-11
Contact:
Hongjun LI, Zhen GU
摘要:
合成生物学与纳米生物学的交叉融合业已成为促进生物技术与生物医药领域发展的重要方向之一。利用合成生物学技术可以帮助生物源性纳米材料创造特殊的结构与功能,驱动纳米生物学的发展。纳米技术的应用则可助力基因线路递送,提升基于合成生物学的生产效率;参与介导基因调控,拓展合成生物学技术的应用场景。合成生物学和纳米生物学的融合可以构建出纳米级功能模块和纳米人工杂合系统,增强改造后体系的功能。本文将着重介绍近期合成生物学和纳米生物学交叉融合的相关研究进展,从纳米技术为合成生物学的发展赋能、合成生物学成为助力纳米技术应用的新引擎以及合成生物学和纳米生物学融合发展这三个角度,着重阐述该领域近期的重点工作,剖析并展望相关技术在基因编辑、药物递送以及医学成像等生物医药领域的应用和前景。未来,合成生物学和纳米生物学的交叉融合可能朝着模块化、标准化、仿生化、功能集成化和智能化的方向进一步发展,为生物医药领域带来新的突破。
中图分类号:
郑涵奇, 吴晴, 李洪军, 顾臻. 合成生物学与纳米生物学的交叉融合及其在生物医药领域的应用[J]. 合成生物学, 2022, 3(2): 279-301.
Hanqi ZHENG, Qing WU, Hongjun LI, Zhen GU. Integration of synthetic biology and nanobiotechnology for biomedical applications[J]. Synthetic Biology Journal, 2022, 3(2): 279-301.
载体类型 | 载体材料 | 递送目标类别 | 特征 | 参考 文献 |
---|---|---|---|---|
有机纳米载体 | 两性离子氨基脂质纳米颗粒 | 长RNA(含Cas9 mRNA、sgRNA) | 可以将多个长RNA打包递送,有望提供DNA修复模板来介导HDR(同源介导的双链DNA修复)基因校正 | [ |
基于卵磷脂的纳米脂质体 | Cas9/sgRNA RNP | 高生物相容性、低细胞毒性和高溶液稳定性 | [ | |
基于可电离脂质的脂质纳米颗粒 | Cas9-sgRNA质粒 | 促进膜融合、膜破裂和内涵体逃逸 | [ | |
可生物还原的脂质纳米颗粒 | Cas9/sgRNA RNP, Cas9 mRNA/sgRNA | 响应还原性细胞内环境,更有效释放RNA和蛋白质 | [ | |
转铁蛋白修饰的脂质体 | DNA | 将功能蛋白的肿瘤靶向潜力和优异的基因递送性能相结合 | [ | |
超支化阳离子聚(β-氨基酯) | Cas9/sgRNA RNP | 能以不同表面电荷实现分子量在一定范围内的蛋白质的胞质递送 | [ | |
氟化酸不稳定支链富羟基聚阳离子 | Cas9-sgRNA质粒 | 良好的pH响应降解性、生物相容性 | [ | |
乳糖衍生的支链阳离子生物聚合物 | Cas9-sgRNA质粒 | 优异的降解性、生物相容性、基因转染性能和肝癌细胞靶向能力 | [ | |
聚(二硫化物) | DNA、mRNA和RNP三种形式的CRISPR-Cas9 | 极大限度地减少了不可降解聚合物载体常见的细胞毒性 | [ | |
阳离子α-螺旋多肽 | Cas9质粒/sgRNA | 具有作为高效基因载体和细胞膜穿透剂的双重功能 | [ | |
无机纳米载体 | 金纳米粒 | Cas9/sgRNA RNP,DNA, Cas9-sgRNA质粒 | 具有独特的光学和结构特性,可以作为基因递送的多功能平台 | [ |
镧系元素掺杂的上转换纳米粒子 | Cas9/sgRNA RNP | 作为纳米传感器,可以通过光来远程控制基因编辑工具的释放 | [ | |
纳米级沸石咪唑骨架 | 质粒DNA,Cas9/sgRNA RNP | 在内涵体pH下质子化,促进内涵体逃逸,增强了向细胞核的递送 | [ | |
功能化的介孔二氧化硅颗粒 | Cas9/sgRNA RNP | 具有高表面积和可调节的孔径,可以和修饰硼酸基团的蛋白质形成配位和静电相互作用,提高向细胞内递送的效率 | [ | |
生物仿生 纳米载体 | 细胞膜衍生纳米囊泡 | 质粒cDNA | MSC纳米囊泡具有生物相容性,并保留了MSC对各种肿瘤细胞的表面相关靶向能力 | [ |
细胞外囊泡 | CRISPR/Cas9质粒,Cas9/sgRNA RNP | 可以被修饰改造以实现靶向递送 | [ | |
DNA纳米线球 | Cas9/sgRNA RNP | DNA纳米线球和sgRNA引导序列之间部分互补时能实现更高效率的基因编辑 | [ | |
病毒样颗粒 | Cas9/sgRNA RNP | 实现瞬时快速递送,并降低脱靶率 | [ |
表1 用于基因线路/编辑体系递送的典型载体
Tab. 1 Representative carriers used for delivering gene circuits/genome editing systems
载体类型 | 载体材料 | 递送目标类别 | 特征 | 参考 文献 |
---|---|---|---|---|
有机纳米载体 | 两性离子氨基脂质纳米颗粒 | 长RNA(含Cas9 mRNA、sgRNA) | 可以将多个长RNA打包递送,有望提供DNA修复模板来介导HDR(同源介导的双链DNA修复)基因校正 | [ |
基于卵磷脂的纳米脂质体 | Cas9/sgRNA RNP | 高生物相容性、低细胞毒性和高溶液稳定性 | [ | |
基于可电离脂质的脂质纳米颗粒 | Cas9-sgRNA质粒 | 促进膜融合、膜破裂和内涵体逃逸 | [ | |
可生物还原的脂质纳米颗粒 | Cas9/sgRNA RNP, Cas9 mRNA/sgRNA | 响应还原性细胞内环境,更有效释放RNA和蛋白质 | [ | |
转铁蛋白修饰的脂质体 | DNA | 将功能蛋白的肿瘤靶向潜力和优异的基因递送性能相结合 | [ | |
超支化阳离子聚(β-氨基酯) | Cas9/sgRNA RNP | 能以不同表面电荷实现分子量在一定范围内的蛋白质的胞质递送 | [ | |
氟化酸不稳定支链富羟基聚阳离子 | Cas9-sgRNA质粒 | 良好的pH响应降解性、生物相容性 | [ | |
乳糖衍生的支链阳离子生物聚合物 | Cas9-sgRNA质粒 | 优异的降解性、生物相容性、基因转染性能和肝癌细胞靶向能力 | [ | |
聚(二硫化物) | DNA、mRNA和RNP三种形式的CRISPR-Cas9 | 极大限度地减少了不可降解聚合物载体常见的细胞毒性 | [ | |
阳离子α-螺旋多肽 | Cas9质粒/sgRNA | 具有作为高效基因载体和细胞膜穿透剂的双重功能 | [ | |
无机纳米载体 | 金纳米粒 | Cas9/sgRNA RNP,DNA, Cas9-sgRNA质粒 | 具有独特的光学和结构特性,可以作为基因递送的多功能平台 | [ |
镧系元素掺杂的上转换纳米粒子 | Cas9/sgRNA RNP | 作为纳米传感器,可以通过光来远程控制基因编辑工具的释放 | [ | |
纳米级沸石咪唑骨架 | 质粒DNA,Cas9/sgRNA RNP | 在内涵体pH下质子化,促进内涵体逃逸,增强了向细胞核的递送 | [ | |
功能化的介孔二氧化硅颗粒 | Cas9/sgRNA RNP | 具有高表面积和可调节的孔径,可以和修饰硼酸基团的蛋白质形成配位和静电相互作用,提高向细胞内递送的效率 | [ | |
生物仿生 纳米载体 | 细胞膜衍生纳米囊泡 | 质粒cDNA | MSC纳米囊泡具有生物相容性,并保留了MSC对各种肿瘤细胞的表面相关靶向能力 | [ |
细胞外囊泡 | CRISPR/Cas9质粒,Cas9/sgRNA RNP | 可以被修饰改造以实现靶向递送 | [ | |
DNA纳米线球 | Cas9/sgRNA RNP | DNA纳米线球和sgRNA引导序列之间部分互补时能实现更高效率的基因编辑 | [ | |
病毒样颗粒 | Cas9/sgRNA RNP | 实现瞬时快速递送,并降低脱靶率 | [ |
细菌 | 细菌改造 | 修饰纳米材料 | 效能 | 参考文献 |
---|---|---|---|---|
Magnetococcus marinus MC-1 | 包含一串磁性氧化铁纳米晶体 | 含药物纳米脂质体 | 磁引导细菌将含药纳米脂质体运输到SCID Beige小鼠HCT116异种移植结直肠肿瘤的缺氧区 | [ |
S. typhimurium VNP20009 | 兼性厌氧,减毒营养缺陷型突变体 | PLGA纳米粒 | 将纳米颗粒在BALB/c小鼠的4T1乳腺癌原位模型中的保留和分布提高100倍 | [ |
S. typhimurium ELH1301, E. coli Nissle 1917 | 具有编码气体囊泡的工程基因簇 | 蛋白质外壳的纳米气体囊泡 | 超声波报告基因工程,用于超声成像 | [ |
E. coli MG1655 | 过表达呼吸链酶Ⅱ(NDH-Ⅱ) | 磁性Fe3O4纳米粒子 | 在BALB/c小鼠的CT 26结肠癌部位原位催化产生H2O2,诱导肿瘤细胞死亡 | [ |
E. coli MG1655 | 表达硝酸盐/亚硝酸盐还原酶 | 碳点掺杂氮化碳 | 光控细菌代谢物疗法,光照射下生成NO抑制BALB/c小鼠4T1肿瘤生长 | [ |
E. coli | 过表达过氧化氢酶 | 含Ce6涂层的聚多巴胺纳米粒 | NIR光照射下实现光热疗法和光动力疗法,在荷瘤BALB/c裸鼠中抑制肿瘤生长 | [ |
S. typhimurium YB1 | 缺氧靶向 | 载有吲哚菁绿(ICG)的纳米颗粒 | 在NIR激光照射下,产生光热杀伤能力,根除C57 BL/6小鼠的MB49实体瘤 | [ |
Magnetococcus marinus AMB-1 | 趋磁性和缺氧靶向 | 光触发的吲哚菁绿纳米粒子 | 磁驱动富集到肿瘤部位,光热疗法消除MCF-7荷瘤BALB/c裸鼠中的肿瘤 | [ |
表2 代表性的工程化细菌-纳米组件杂合系统
Tab. 2 Representative hybrid systems of engineered bacteria and nanocomponents
细菌 | 细菌改造 | 修饰纳米材料 | 效能 | 参考文献 |
---|---|---|---|---|
Magnetococcus marinus MC-1 | 包含一串磁性氧化铁纳米晶体 | 含药物纳米脂质体 | 磁引导细菌将含药纳米脂质体运输到SCID Beige小鼠HCT116异种移植结直肠肿瘤的缺氧区 | [ |
S. typhimurium VNP20009 | 兼性厌氧,减毒营养缺陷型突变体 | PLGA纳米粒 | 将纳米颗粒在BALB/c小鼠的4T1乳腺癌原位模型中的保留和分布提高100倍 | [ |
S. typhimurium ELH1301, E. coli Nissle 1917 | 具有编码气体囊泡的工程基因簇 | 蛋白质外壳的纳米气体囊泡 | 超声波报告基因工程,用于超声成像 | [ |
E. coli MG1655 | 过表达呼吸链酶Ⅱ(NDH-Ⅱ) | 磁性Fe3O4纳米粒子 | 在BALB/c小鼠的CT 26结肠癌部位原位催化产生H2O2,诱导肿瘤细胞死亡 | [ |
E. coli MG1655 | 表达硝酸盐/亚硝酸盐还原酶 | 碳点掺杂氮化碳 | 光控细菌代谢物疗法,光照射下生成NO抑制BALB/c小鼠4T1肿瘤生长 | [ |
E. coli | 过表达过氧化氢酶 | 含Ce6涂层的聚多巴胺纳米粒 | NIR光照射下实现光热疗法和光动力疗法,在荷瘤BALB/c裸鼠中抑制肿瘤生长 | [ |
S. typhimurium YB1 | 缺氧靶向 | 载有吲哚菁绿(ICG)的纳米颗粒 | 在NIR激光照射下,产生光热杀伤能力,根除C57 BL/6小鼠的MB49实体瘤 | [ |
Magnetococcus marinus AMB-1 | 趋磁性和缺氧靶向 | 光触发的吲哚菁绿纳米粒子 | 磁驱动富集到肿瘤部位,光热疗法消除MCF-7荷瘤BALB/c裸鼠中的肿瘤 | [ |
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