Confined growth of ZIF-8 in dendritic mesoporous organosilica nanoparticles as bioregulators for enhanced mRNA delivery in vivo

Yue Wang; Hao Song; Chao Liu; Ye Zhang; Yueqi Kong; Jie Tang; Yannan Yang; Chengzhong Yu

doi:10.1093/nsr/nwaa268

Confined growth of ZIF-8 in dendritic mesoporous organosilica nanoparticles as bioregulators for enhanced mRNA delivery in vivo

Natl Sci Rev. 2020 Oct 23;8(8):nwaa268. doi: 10.1093/nsr/nwaa268. eCollection 2021 Aug.

Authors

Yue Wang¹, Hao Song¹, Chao Liu², Ye Zhang², Yueqi Kong¹, Jie Tang¹, Yannan Yang¹, Chengzhong Yu¹

Affiliations

¹ Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia.
² School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, China.

Abstract

Zeolitic imidazolate framework-8 (ZIF-8) and its composites have diverse applications. However, ZIF-8-based nanocomposites are mainly used as carriers in biomolecular delivery, with the functions of metal ions and ligands rarely used to modulate the biofunctions. In this work, dendritic mesoporous organosilica nanoparticles (DMONs) with tetrasulfide bond were used to confine ZIF-8 growth partially inside mesopores as a novel nanocomposite for mRNA delivery. Each component in the resultant DMONs-ZIF-8 contributed to mRNA delivery applications, including high loading benefitting from positively charged ZIF-8 and large mesopores of DMONs, endosomal escape promoted by the imidazole ring of ZIF-8, and long-term glutathione depletion mediated by both zinc ions and tetrasulfide bond. Combined together, DMONs-ZIF-8 demonstrated enhanced mRNA translation and better transfection efficiency than commercial products and toxic polymer-modified DMONs in vitro and in vivo.

Keywords: bioregulator; cellular delivery; mRNA transfection; mesoporous organosilica nanoparticles; metal-organic framework.