Efficient Cytosolic Delivery Using Crystalline Nanoflowers Assembled from Fluorinated Peptoids

Abstract The design and synthesis of biocompatible nanomaterials as cargoes for the intracellular delivery of therapeutic proteins or genes have attracted intense attention because of their potential for use in therapeutics. Despite the advances in this area, very few nanomaterials can be efficiently delivered to the cytosol. To address these challenges, crystalline nanoflower‐like particles are designed and synthesized from fluorinated sequence‐defined peptoids; the crystallinity and fluorination of these particles enable highly efficient cytosolic delivery with minimal cytotoxicity. A cytosol delivery rate of 80% has been achieved for the fluorinated peptoid nanoflowers. Furthermore, these nanocrystals can carry therapeutic genes, such as mRNA and effectively deliver the payload into the cytosol, demonstrating the universal delivery capability of the nanocrystals. The results indicate that self‐assembly of crystalline nanomaterials from fluorinated peptoids paves a new way toward development of nanocargoes with efficient cytosolic gene delivery capability.