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Research Article

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

Wenxing Lv1,3, Ziwei Han2( ), Shaokun Dong1,3, Yanjuan Huang1,3, Jinqi Deng1,3, Chao Liu1,3, Qiang Feng1,4( ), Jiashu Sun1,2,3( )
Beijing Engineering Research Center for BioNanotechnology, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, National Center for Nanoscience and Technology, Beijing 100190, China
Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China
University of Chinese Academy of Sciences, Beijing 100049, China
Department of Pharmacology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas 75390, USA
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Graphical Abstract

We report a microfluidic reactor for one-step, ultrafast synthesis of size-tunable protein-loaded ZIF-8 nanoparticles in aqueous phase.

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.

Keywords

microfluidicszeolitic imidazolate framework-8nanoparticlessize tunableprotein delivery

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Nano Research
Volume 16 Issue 12,
December 2023
Pages 13409-13418
DOI: 10.1007/s12274-023-6213-x
Cite this article:
Lv W, Han Z, Dong S, et al. Microfluidic one-step, aqueous synthesis of size-tunable zeolitic imidazolate framework-8 for protein delivery. Nano Research, 2023, 16(12): 13409-13418. https://doi.org/10.1007/s12274-023-6213-x
Topics:
Organic frameworks
Part of a topical collection:
Special issue for the 20th Anniversary of NCNST

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Received: 03 July 2023
Revised: 14 September 2023
Accepted: 18 September 2023
Published: 16 October 2023
© Tsinghua University Press 2023
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