Stimuli-Responsive Proteinosomes Based on Biohybrid Shell Cross-Linked Micelles

Area of Science:

• Biomaterials Science
• Nanotechnology
• Polymer Chemistry

Background:

• Developing stimuli-responsive drug delivery systems is crucial for targeted therapies.
• Protein-based nanostructures offer biocompatibility but require robust fabrication methods.

Purpose of the Study:

• To create novel stimuli-responsive proteinosomes using a shell-crosslinked micelle template.
• To evaluate the structural integrity, activity, and release kinetics of encapsulated proteins.
• To assess the in vitro biocompatibility and cellular uptake of the fabricated proteinosomes.

Main Methods:

• Synthesis of a thermoresponsive diblock copolymer (PDEGMA-b-P(PEGMA-co-PDSMA)).
• Self-assembly into micelles and cross-linking of shells with bovine serum albumin (BSA) via disulfide bonds.
• Dissolution of core to form proteinosomes and characterization of their properties (size, structure, thermoresponsiveness).
• Assessment of BSA activity and release triggered by dithiothreitol (DTT).
• In vitro cell viability and cellular uptake assays using NIH 3T3 and 4T1 cells.

Main Results:

• Successfully fabricated stimuli-responsive proteinosomes (approx. 50 nm) with capsule-like structures.
• Encapsulated BSA retained secondary structure and esterase-like activity.
• Protein release was triggered by the addition of DTT, confirming disulfide bond linkage.
• The proteinosomes exhibited a phase transition temperature at 35 °C and showed low toxicity to tested cell lines.
• Efficient cellular uptake was observed in 4T1 cells.

Conclusions:

• A novel and effective method for fabricating stimuli-responsive proteinosomes was established.
• The proteinosomes are biocompatible, thermoresponsive, and capable of controlled protein release.
• These findings highlight the potential of these proteinosomes as advanced drug delivery vehicles.