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.

Principles and Characteristics of Polymerization-Induced Self-Assembly with Various Polymerization Techniques

“…Future PISA methods, with alternative polymerization approaches, will likely allow the efficient preparation of functional nanoparticles (or nanomedicines) that are currently only accessible via the less efficient solvent switch method. For example, efficient synthesis is beneficial for nanoparticles used in antibacterial products, 79,138 treatment of diabetes, [139][140][141][142] drug delivery, [143][144][145][146] magnetic resonance imaging (MRI), 145,[147][148][149] and so forth. New delicate methods to accurately target desired morphologies during PISA are desired to fully utilize the potential of this powerful technique.…”

A Balance Between Capture and Release: How Nanochaperones Regulate Refolding of Thermally Denatured Proteins

“…We illustrated that, in addition to the capture of unfolded clients, the controlled release of immature polypeptides and native proteins plays a fundamental role in refolding. Inspired by this mechanism, we designed new nanochaperone systems for insulin and antigen delivery in vivo [8b,c] . Evidently, a deeper understanding of the new working mechanism of nanochaperones is important for engineering new mimetic systems and realizing their full potential.…”

Insulin Delivery Using Dynamic Covalent Boronic Acid/Ester‐Controlled Release

“…Boronic acid derivatives have been utilised by Ma and co‐workers as synthetic chaperones in the form of glucose responsive mixed‐shell (hydrophilic/hydrophobic) micellar assemblies for insulin protection and delivery. [ 152 ] In their approach the authors drew inspiration from natural assisting proteins that support structural changes of other macromolecules, and were able to draw upon insights gained in previous experience of restoration of amyloid β homeostasis. [ 153 ] By developing synthetic nanochaperones capable of glucose‐sensitive insulin delivery, they have sought to address potential issues with aggregation and fibrillation of insulin in the process of drug encapsulation, storage and release.…”