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Protein delivery with cell-penetrating poly(disulfide)s
Giulio Gasparini1, Stefan Matile1
1School of Chemistry and Biochemistry, NCCR Chemical Biology, University of Geneva, Geneva, Switzerland. stefan.matile@unige.ch.
Chemical Communications (Cambridge, England)
|October 13, 2015
Summary
This study introduces a novel, non-toxic method using cell-penetrating poly(disulfide)s and biotin-streptavidin technology for direct protein delivery, bypassing endosomal capture for enhanced cellular uptake.
Area of Science:
- Biotechnology
- Cellular Biology
- Drug Delivery
Background:
- Endosomal capture limits the efficiency of intracellular protein delivery.
- Developing non-toxic, generalizable methods for direct protein delivery is crucial for therapeutic applications.
Purpose of the Study:
- To develop a simple, non-toxic method for direct protein delivery into cells.
- To overcome endosomal entrapment and achieve efficient protein delivery, including to the nucleoli.
Main Methods:
- Utilized cell-penetrating poly(disulfide)s conjugated with biotin.
- Employed the high-affinity biotin-streptavidin interaction for protein targeting.
- Assessed cellular uptake and intracellular localization of delivered proteins.
Main Results:
- The combined system effectively delivered proteins into cells, bypassing significant endosomal capture.
- Direct delivery to cellular compartments, including the nucleoli, was achieved.
- The method demonstrated a general applicability and non-toxic profile.
Conclusions:
- The poly(disulfide)-biotin-streptavidin system offers a simple, non-toxic, and efficient strategy for direct protein delivery.
- This approach overcomes a major hurdle in intracellular delivery, enabling access to various cellular compartments.
