mRNA therapeutics are set to revolutionize disease prevention and treatment, inspiring the development of platforms for safe and effective mRNA delivery. However, most mRNA delivery platforms, including lipid nanoparticles (the most advanced delivery modality for nucleic acids), contain cationic components, which can induce inflammation and long-term toxicity. Furthermore, there is also a pressing need for a versatile delivery modality that can readily accommodate a wide array of therapeutic payloads. Here, I will present a non-cationic, versatile, and biocompatible bioactive metal–organic nanoparticle platform, whereby a myriad types of therapeutics, including mRNA1, functional small molecules2, and proteins3, can be readily assembled into a polymer-polyphenol network stabilized by metal ions. This platform preserves the functionality of incorporated payloads, enabling application in gene expression and editing, bioimaging, and HIV latency reversal. Notably, these bioactive metal–organic nanoparticles can be readily scaled up using the Micropore PathFinder system, highlighting the potential of their translatability. The versatility and bioactivity of the platform open a promising avenue for the rational design of future bioactive materials and nanoparticle-mediated therapeutic delivery systems.
Reference
1. Gu, Chen et al. Nat. Commun. 2024, 15, 9664
2. Chen et al. Angew. Chemie. Int. Ed. 2024, 63, e202319583
3. Chen et al. Adv. Mater. 2022, 34, 2108624