Nanochaperones Mediated Delivery of Insulin.

Abstract

Insulin would undergo unfolding and fibrillation under stressed conditions, which may cause serious biotechnological and medical problems. Herein, by mimicking the structure and functions of natural chaperones HSP70s, self-assembled polymeric micelles are used as nanochaperones for the delivery of insulin. The confined hydrophobic domains on the surface of nanochaperones adsorb partially unfolded insulin, inhibiting the aggregation and fibrillation and enhancing the stability of insulin. The bioactivity of insulin is well-reserved after incubation with the nanochaperones at 37 °C for 7 d or heating at 70 °C for 1 h. The stealthy poly(ethylene glycol) chains around the confined domains protect the adsorbed insulin from enzymatic degradation and prolong the circulation time. More importantly, the excellent glucose sensitivity of the hydrophobic domains enables the nanochaperones to release and refold insulin in native form in response to hyperglycemia. This kind of nanochaperone may offer a hopeful strategy for the protection and delivery of insulin.