Polymeric Nanoparticles Amenable to Simultaneous Installation of Exterior Targeting and Interior Therapeutic Proteins

Effective delivery of therapeutic proteins is a formidable challenge. Herein, using a unique polymer family with a wide-ranging set of cationic and hydrophobic features, we developed a novel nanoparticle (NP) platform capable of installing protein ligands on the particle surface and simultaneously carrying therapeutic proteins inside by a self-assembly procedure. The loaded therapeutic proteins (e.g., insulin) within the NPs exhibited sustained and tunable release, while the surface-coated protein ligands (e.g., transferrin) were demonstrated to alter the NP cellular behaviors. In vivo results revealed that the transferrin-coated NPs can effectively be transported across the intestinal epithelium for oral insulin delivery, leading to a notable hypoglycemic response.National Institutes of Health (U.S.) (Grants EB015419, R00CA160350, and CA151884)Prostate Cancer Foundation (Challenge Award)National Research Foundation of Korea (Grant K1A1A2048701)David H. Koch Institute for Integrative Cancer Research at MIT. Prostate Cancer Foundation Program in Cancer NanotherapeuticsNational Natural Science Foundation (China) (Grant 81173010