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

Inspired from heat shock proteins (HSPs), a thermo-sensitive coacervate-forming polycaprolactone (CPCL) was designed as a natural chaperone mimic to protect proteins from thermal stress. Unlike the coil-globule polymers of poly(N-isopropyl acrylamide) (PNIPAM), the as-designed CPCL underwent a partial dehydration during heating, characterizing it as a coacervate-forming polymer. With its ability to transform between the coil and coacervate states in response to temperature, theCPCL spontaneously captured and released targeted proteins, thereby 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 (T_m). Taken together, we envision that the CPCL with excellent biodegradability and biocompatibility could be a safe excipient for protein protection against thermal damage without separation.