Direct Delivery of Functional Proteins and Enzymes to the Cytosol Using Nanoparticle-Stabilized Nanocapsules Rui Tang Chang Soo Kim David J. Solfiell Subinoy Rana Rubul Mout Elih M. Velázquez-Delgado Apiwat Chompoosor Youngdo Jeong Bo Yan Zheng-Jiang Zhu Chaekyu Kim Jeanne A. Hardy Vincent M. Rotello 10.1021/nn402753y.s001 https://acs.figshare.com/articles/journal_contribution/Direct_Delivery_of_Functional_Proteins_and_Enzymes_to_the_Cytosol_Using_Nanoparticle_Stabilized_Nanocapsules/2383636 Intracellular protein delivery is an important tool for both therapeutic and fundamental applications. Effective protein delivery faces two major challenges: efficient cellular uptake and avoiding endosomal sequestration. We report here a general strategy for direct delivery of functional proteins to the cytosol using nanoparticle-stabilized capsules (NPSCs). These NPSCs are formed and stabilized through supramolecular interactions between the nanoparticle, the protein cargo, and the fatty acid capsule interior. The NPSCs are ∼130 nm in diameter and feature low toxicity and excellent stability in serum. The effectiveness of these NPSCs as therapeutic protein carriers was demonstrated through the delivery of fully functional caspase-3 to HeLa cells with concomitant apoptosis. Analogous delivery of green fluorescent protein (GFP) confirmed cytosolic delivery as well as intracellular targeting of the delivered protein, demonstrating the utility of the system for both therapeutic and imaging applications. 2013-08-27 00:00:00 HeLa cells cytosolic delivery acid capsule protein carriers Functional Proteins Analogous delivery Direct Delivery supramolecular interactions Effective protein delivery protein cargo NPSC endosomal sequestration imaging applications GFP