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Microfluidic one-step, aqueous synthesis of size-tunable zeolitic imidazolate framework-8 for protein delivery

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Abstract

Zeolitic imidazolate framework-8 (ZIF-8) with porous structure, biocompatibility, and pH-sensitive release behavior is a promising nanoplatform for protein delivery. However, it is still a challenging task for a practical synthesis of protein-loaded ZIF-8 nanoparticles. Here we report an all-aqueous microfluidic reactor for one-step, rapid, and highly controlled synthesis of ZIF-8 nanoparticles with high protein loading at room temperature. Microfluidic reactor allows for an ultrafast (< 35 ms), complete mixing of Zn2+ ions and 2-methylimidazole (2-MIM) at different molecular ratios, leading to the formation of stable ZIF-8 nanoparticles with tunable sizes (13.2–191.4 nm) in less than 30 s. By pre-mixing various proteins such as bovine serum albumin (BSA) (isoelectric point (pI) = 5.82), ovalbumin (OVA) (pI = 4.82), or RNase A (pI = 8.93) with 2-MIM, ZIF-8 nanoparticles can be synthesized with protein encapsulation efficiency over 97%. Among the nanoparticles with different sizes, 25 nm ZIF-8 nanoparticles show the best performance in promoting the cellular uptake of protein payload. Using OVA as a model protein, we demonstrate that 25 nm ZIF-8 nanoparticles significantly enhance the cytosolic delivery of antigen, as indicated by the effective activation of dendritic cells. We anticipate that this microfluidic synthesis of nanomaterials may advance the emerging field of cytosolic protein delivery.

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Acknowledgements

This work was supported by the National Key R&D Program of China (Nos. 2020YFA0210800 and 2021YFA0909400), the National Natural Science Foundation of China (Nos. 22025402, 22227805, T2222008, and 22174030), The Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDB36020300), and CAS Project for Young Scientists in Basic Research (No. YSBR-036).

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Authors and Affiliations

  1. Beijing Engineering Research Center for BioNanotechnology, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, National Center for Nanoscience and Technology, Beijing, 100190, China

    Wenxing Lv, Shaokun Dong, Yanjuan Huang, Jinqi Deng, Chao Liu, Qiang Feng & Jiashu Sun

  2. Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China

    Ziwei Han & Jiashu Sun

  3. University of Chinese Academy of Sciences, Beijing, 100049, China

    Wenxing Lv, Shaokun Dong, Yanjuan Huang, Jinqi Deng, Chao Liu & Jiashu Sun

  4. Department of Pharmacology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, 75390, USA

    Qiang Feng

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  1. Wenxing Lv
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  3. Shaokun Dong
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Correspondence to Ziwei Han, Qiang Feng or Jiashu Sun.

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12274_2023_6213_MOESM1_ESM.pdf

Electronic Supplementary Material: Microfluidic one-step, aqueous synthesis of size-tunable zeolitic imidazolate framework-8 for protein delivery

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Lv, W., Han, Z., Dong, S. et al. Microfluidic one-step, aqueous synthesis of size-tunable zeolitic imidazolate framework-8 for protein delivery. Nano Res. 16, 13409–13418 (2023). https://doi.org/10.1007/s12274-023-6213-x

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