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

Area of Science:

• Biomaterials Science
• Drug Delivery
• Nanotechnology

Background:

• Protein therapeutics offer high specificity and low toxicity but face delivery challenges due to protein instability and complex properties.
• Selecting appropriate polymers for protein delivery is complicated by the intricate nature of both proteins and polymers.

Purpose of the Study:

• To develop a high-throughput screening platform (ProMatch) for efficient data collection on protein-polymer interactions.
• To streamline polymer selection for targeted protein delivery systems.
• To demonstrate the platform's utility in developing specific therapeutic delivery systems.

Main Methods:

• A fluorescence-based high-throughput screening platform (ProMatch) was developed to assess protein-polymer interactions.
• In vivo and in vitro experiments were conducted with rational design based on screening results.
• Commercially available polymers were screened for targeted protein delivery applications.

Main Results:

• ProMatch successfully expedited the identification of promising polymer candidates for tissue-specific protein delivery.
• A polyhexamethylene biguanide (PHMB)-based system was developed for delivering proteins to white adipose tissue for obesity treatment.
• A branched polyethylenimine (bPEI)-based system was created for neuron-specific protein delivery to promote optic nerve regeneration.

Conclusions:

• The ProMatch platform significantly accelerates the discovery of suitable polymers for protein delivery.
• This methodology provides a robust foundation for developing novel protein-based therapeutics with targeted delivery capabilities.
• The developed systems demonstrate the potential of ProMatch in creating innovative solutions for challenging medical conditions.