Journal
ACS NANO
Volume 7, Issue 8, Pages 6667-6673Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nn402753y
Keywords
nanoparticle; nanocapsule; intracellular protein delivery; supramolecular assembly; organelle targeting
Categories
Funding
- NIH [GM077173, EB014277, GM80532]
- NIH CBI [S11110000000104]
- National Science Foundation [S21000025700000, DGE-0504485]
- Direct For Biological Sciences
- Div Of Biological Infrastructure [1126366] Funding Source: National Science Foundation
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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 similar to 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.
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