PNNL

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 promise for use in therapeutics. Despite the advances in this area, very few nanomaterials can be efficiently delivered to the cytosol. To address these challenges, we designed and synthesized crystalline nanoflower-like particles from fluorinated sequence-defined peptoids; the crystallinity and fluorination of these particles enabled highly efficient cytosolic delivery with minimal cytotoxicity. We delivered these particles, 80% appear to diffuse in the cytosol. Furthermore, these nanocrystals can carry mRNA for instance and effectively delivered into cytosol for gene transfection, demonstrating the generality of our nanocrystals. Our results indicate that self-assembly of crystalline nanomaterials from fluorinated peptoids paves a new way toward development of nanocargoes with efficient cytosol gene delivery. Y. Song and M. Wang contributed equally to this work. This work was supported by start-up funds from Washington State University. Peptoid synthesis work was supported by the Materials Synthesis and Simulation Across Scales (MS3) Initiative through the LDRD fund at Pacific Northwest National Laboratory (PNNL). Assembly of peptoid particles and their structural characterizations were supported by the U.S. Department of Energy, Office of Basic Energy Sciences, Biomolecular Materials Program at PNNL. XRD work was conducted at the Advanced Light Source with support from the Molecular Foundry, at Lawrence Berkeley National Laboratory, both of which are supported by the Office of Science, under Contrast No. DE-AC02-05CH11231. PNNL is multi-program national laboratory operated for Department of Energy by Battelle under Contract No. DE-AC05-76RL01830.