(230b) Nanocapsules for Protein Delivery

An average cell contains thousands of proteins participating in its normal cellular functions. Most diseases, however, are somehow related to the malfunction of specific proteins. Protein therapy, endowed with more defined action mechanism than small molecule drugs and safer administration methods than gene therapy, is considered to be a treatment modality of choice for many disorders today and in the future. Advances in biotechnology have accelerated the economical, large-scale production of proteins, vaccines, and hormones, making them readily available for therapeutic applications in medical practices and clinical studies. Up to now, over 140 FDA-approved protein drugs have been placed on the market, and more are coming.  Despite its fast growth in the recent years, protein therapy still faces critical challenges, such as poor in-vitro and in-vivo stability, fast degradation and clearance, and the incapability to delivery proteins across biological barriers. Developing efficient protein delivery strategy is still in high demand. Various factors affect the efficiency of protein delivery agents, including surface properties, size, and shape. To develop protein delivery agents for various therapeutic applications, we designed a general strategy based on protein nano-encapsulation, a novel protein-polymer conjugation technique achieved by in-situ polymerization on protein surface. This approach yielded protein nanocapsules with retained activity, enhanced stability and the ability to transport through biological barriers (such as cell membranes). This strategy is applicable over a variety of proteins, for a wide spectrum of therapeutic applications. Our in-vitro and in-vivo experiments demonstrated the potential of the nano-encapsulation strategy for the treatment of gout, phenylketonuria, alcohol intoxication, and other therapeutic applications.