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

Inspired by heat shock proteins (HSPs), thermo-sensitive coacervate-forming polycaprolactone (CPCL) was designed as natural chaperone mimics to protect proteins from thermal stress. Different from coil-globule polymers of poly(N-isopropyl acrylamide) (PNIPAM), the CPCL underwent a partial dehydration during heating, characterized as a coacervate-forming polymer. With the ability to transform between coil and coacervate state in response to temperature, this CPCL could spontaneously capture and release targeted protein, behaving like a natural chaperone of HSPs. Remarkably, compared with the PNIPAM homopolymer, the CPCL provided more efficient protection for proteins by inhibiting heat-induced aggregation above the melting temperature (Tm). Taken together, we envisioned that this CPCL with excellent biodegradability and biocompatibility could be a safe excipient for protein protection against thermal damage without separation.