Thermo-sensitive polycaprolactone coacervates for preventing protein aggregation under thermal stress

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Protein Engineering

Background:

• Heat shock proteins (HSPs) are crucial for cellular protection against thermal stress.
• Existing synthetic polymers like poly(N-isopropyl acrylamide) (PNIPAM) have limitations in protein protection.
• There is a need for safe and effective biomaterials that mimic natural chaperone functions.

Purpose of the Study:

• To design and synthesize a thermo-sensitive coacervate-forming polycaprolactone (CPCL) as a natural chaperone mimic.
• To evaluate the protein protection capabilities of CPCL against thermal stress.
• To assess the potential of CPCL as a safe excipient for protein stabilization.

Main Methods:

• Synthesis of thermo-sensitive coacervate-forming polycaprolactone (CPCL).
• Characterization of CPCL's coil-to-coacervate state transition upon heating.
• Assessment of CPCL's ability to capture and release proteins in response to temperature changes.
• Evaluation of protein aggregation inhibition by CPCL compared to PNIPAM.

Main Results:

• CPCL demonstrated a unique partial dehydration and coacervate formation upon heating, unlike PNIPAM.
• CPCL effectively captured and released targeted proteins, functioning as a temperature-responsive biomaterial.
• CPCL significantly inhibited heat-induced protein aggregation more efficiently than PNIPAM above its melting temperature.
• The synthesized CPCL exhibited excellent biodegradability and biocompatibility.

Conclusions:

• The designed CPCL acts as an effective natural chaperone mimic, protecting proteins from thermal damage.
• CPCL's thermo-responsive coacervate formation enables spontaneous protein capture and release.
• CPCL shows promise as a safe and biodegradable excipient for protein stabilization in various applications.
• This study highlights the potential of coacervate-forming polymers in biomimetic applications for protein protection.