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Cytosolic protein delivery using pH-responsive, charge-reversible lipid nanoparticles
Yusuke Hirai1, Hisaaki Hirose1, Miki Imanishi1
1Institute for Chemical Research, Kyoto University, Uji, Kyoto, 611-0011, Japan.
Scientific Reports
|October 7, 2021
Summary
Dioleoylglycerophosphate-diethylenediamine (DOP-DEDA) based lipid nanoparticles (LNPs) effectively deliver proteins into cells. This study demonstrates efficient encapsulation and cytosolic release of proteins using these pH-responsive LNPs for biopharmaceutical applications.
Area of Science:
- Biotechnology
- Drug Delivery
- Nanomedicine
Background:
- Proteins are valuable biopharmaceuticals but face delivery challenges into cells.
- Lipid nanoparticles (LNPs) offer a promising solution for intracellular delivery.
- Key challenges include LNP formulation, protein encapsulation, and endosomal escape.
Purpose of the Study:
- To assess the efficacy of Dioleoylglycerophosphate-diethylenediamine (DOP-DEDA) based LNPs for intracellular protein delivery.
- To overcome limitations in protein delivery systems using pH-responsive, charge-reversible lipids.
Main Methods:
- Formulation of DOP-DEDA based LNPs with controlled particle size (<200 nm) and low dispersity (<0.2).
- Encapsulation of a negatively charged green fluorescent protein (GFP) analog into the formulated LNPs.
- Evaluation of cellular uptake and cytosolic release of the encapsulated protein in treated cells.
Main Results:
- Successful encapsulation of approximately 80% of the cargo protein into DOP-DEDA LNPs.
- LNPs achieved desired particle size and polydispersity index, crucial for formulation.
- Over 90% of treated cells showed cytosolic distribution of fluorescent protein signals, indicating efficient delivery.
Conclusions:
- DOP-DEDA based LNPs are effective for intracellular protein delivery.
- The pH-responsive nature of DOP-DEDA facilitates endosomal escape and cytosolic release.
- This LNP system shows significant potential for advancing protein-based biopharmaceuticals.
