Redox-responsive nanocapsules for intracellular protein delivery

Area of Science:

• Biotechnology
• Nanotechnology
• Cell Biology

Background:

• Direct protein delivery to the cytosol is crucial for various biological and medical applications.
• Controlled release vehicles are needed for effective intracellular protein delivery.

Purpose of the Study:

• To engineer redox-responsive single-protein nanocapsules for efficient intracellular protein delivery.
• To demonstrate the controlled release of protein cargo within the cell cytosol.
• To evaluate the therapeutic potential of this delivery system in cancer treatment.

Main Methods:

• In situ interfacial polymerization to encapsulate proteins within a positively-charged polymeric shell.
• Disulfide-containing crosslinkers were used to create redox-responsive shells.
• Cell-free assays with glutathione (GSH) to confirm shell dissociation.
• Cellular uptake and intracellular protein release studies.
• Delivery of active caspase 3 (CP-3) to induce apoptosis in cancer cell lines.

Main Results:

• Successfully prepared redox-responsive single-protein nanocapsules.
• Confirmed nanocapsule dissociation and protein release under reducing conditions (GSH).
• Demonstrated efficient cellular internalization and cytosolic protein release.
• Showed that delivered active caspase 3 (CP-3) induces apoptosis in HeLa, MCF-7, and U-87 MG cancer cells.

Conclusions:

• Developed an effective strategy for intracellular protein delivery using redox-responsive nanocapsules.
• This approach enables controlled protein release within the reducing cellular environment.
• The nanocapsule system shows promise for therapeutic, diagnostic, and reprogramming applications, particularly in cancer therapy.