Develop Targeted Protein Drug Carriers through a High‐Throughput Screening Platform and Rational Design

Abstract

Protein‐based drugs offer advantages such as high specificity, low toxicity, and minimal side effects compared to small molecule drugs. However, delivery of proteins to target tissues or cells remains challenging due to the instability, diverse structures, charges, and molecular weights of proteins. Polymers have emerged as a leading choice for designing effective protein delivery systems, but identifying a suitable polymer for a given protein is complicated by the complexity of both proteins and polymers. To address this challenge, we developed a fluorescence‐based high‐throughput screening platform called ProMatch to efficiently collect data on protein‐polymer interactions, followed by in vivo and in vitro experiments with rational design. Using this approach to streamline polymer selection for targeted protein delivery, we identified candidate polymers from commercially available options and developed a polyhexamethylene biguanide (PHMB)‐based system for delivering proteins to white adipose tissue as a treatment for obesity. We also developed a branched polyethylenimine (bPEI)‐based system for neuron‐specific protein delivery to stimulate optic nerve regeneration. Our high‐throughput screening methodology expedites identification of promising polymer candidates for tissue‐specific protein delivery systems, thereby providing a platform to develop innovative protein‐based therapeutics.This article is protected by copyright. All rights reserved