Temperature-sensitive Micelles as Artificial Chaperones for Insulin Protection

Abstract

Insulin is an essential and versatile protein taking part in the control of blood glucose levels and protein anabolism. However, under prolonged storage or high temperature stress, insulin tends to unfold and aggregate into toxic amyloid fibrils, leading to loss of physiological function. Inspired by natural chaperones, a series of temperature-sensitive polycaprolactone-based micelles were designed to prevent insulin from deactivation. The micelles were fabricated through the self-assembly of amphiphilic copolymers of methoxy poly(ethylene glycol)-poly(4-diethylformamide caprolactone-co-caprolactone) (mPEG₁₇-P(DECL-co-CL)), which had a regular spherical morphology with particle sizes of about 100 nm. In addition, the lower critical solution temperature (LCST) of the micelles could be tuned to 9 and 29 °C by changing the ratio of DECL to CL. Benefiting from the temperature-sensitivity of DECL segment, the binding ability of micelles to insulin could be modulated by changing the temperature. Above LCST, micelles effectively inhibited insulin aggregation and protected it from thermal inactivation due to the strong binding ability between the hydrophobic segment DECL and insulin. Below LCST, DECL segment returned to hydrophilic and bound weakly with insulin, leading to the release of insulin and assisting in its recovery of secondary structure. Thus, these temperature-sensitive micelles provided an effective strategy for insulin protection.