Structure-Based Nanocarrier Design for Protein Delivery

Structure-based nanocarrier design for protein delivery remains challenging and has rarely been documented in the literature. We herein present a facile computer-aided approach for rational and customized design of a unique linear-dendritic telodendrimer that self-assembles into a nanocarrier for therapeutic protein delivery, e.g., insulin. Virtual screening of a small-molecule library was performed to identify optimal protein binding moieties, which were conjugated precisely in the telodendrimer backbone preinstalled with charged moieties. We systematically tested our hypothesis and obtained significant correlations between the computational predictions and experimental results. The d-α-tocopherol (vitamin E)-containing nanocarrier showed strong binding affinity for insulin in both computational prediction and experiments, which led to improved blood glucose control. This study affirms the concept and validates the approach of structure-based nanocarrier design for protein delivery.