Encapsulation, Visualization and Expression of Genes with Biomimetically Mineralized Zeolitic Imidazolate Framework-8 (ZIF-8)

Encapsulation, Visualization and Expression of Genes with Biomimetically Mineralized Zeolitic Imidazolate Framework-8 (ZIF-8)
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DOI:
10.1002/smll.201902268
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发表时间:
2019-07-01
期刊:
影响因子:
13.3
通讯作者:
Shukla, Ravi
Shukla, Ravi
中科院分区:
材料科学1区
文献类型:
--
作者:
Poddar, Arpita;Conesa, Jose J.;Shukla, Ravi

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最近在生物分子-金属-有机框架(MOF)复合材料方面的研究已被证明是保护蛋白质的有效策略。然而,对于核酸等其他生物大分子来说,纳米MOFs的封装和相关表征还处于起步阶段。本文报道了将完整基因组封装在沸石咪唑酯框架 8 (ZIF-8) MOF 中以及由纳米 MOF 复合材料传递的基因的细胞表达。使用绿色荧光蛋白 (GFP) 质粒 (plGFP) 作为概念验证遗传大分子,显示 plGFP 成功转染哺乳动物癌细胞长达 4 天。细胞转染测定和软 X 射线冷冻断层扫描 (cryo-SXT) 证明了 DNA@MOF 生物复合材料作为细胞内基因传递载体的可行性。表达发生在相对较长的时间点,其中货物核酸逐渐释放以维持持续表达。
Recent work in biomolecule-metal-organic framework (MOF) composites has proven to be an effective strategy for the protection of proteins. However, for other biomacromolecules such as nucleic acids, the encapsulation into nano MOFs and the related characterizations are in their infancy. Herein, encapsulation of a complete gene-set in zeolitic imidazolate framework-8 (ZIF-8) MOFs and cellular expression of the gene delivered by the nano MOF composites are reported. Using a green fluorescent protein (GFP) plasmid (plGFP) as a proof-of-concept genetic macromolecule, successful transfection of mammalian cancer cells with plGFP for up to 4 days is shown. Cell transfection assays and soft X-ray cryo-tomography (cryo-SXT) demonstrate the feasibility of DNA@MOF biocomposites as intracellular gene delivery vehicles. Expression occurs over relatively prolonged time points where the cargo nucleic acid is released gradually in order to maintain sustained expression.