Abstract: Conjugating synthetic polymers to proteins is beneficial in medicine, leading to enhanced materials functional in targeted drug delivery, diagnostics, and as therapeutics.  Loading proteins into nanoparticles has similar advantages. In this context, polymer chains or nanoparticles extend the plasma half-life of a protein and reduce immunogenicity.  In addition,  they can stabilize proteins to storage conditions such as fluctuations in temperature.  Polymers and nanoparticles can also impart new properties to a protein such as a phase change in response to temperature, pH, or molecules.  Such protein-polymer conjugates and nanogels are useful in biotechnology applications.  This talk will focus on responsive polymer conjugates and prodrugs to enhance the therapeutic efficacy of protein and small molecule therapeutics. The rational design, synthesis, and preclinical evaluation of these materials will be discussed.  In addition, we have synthesized new linkers that can release unmodified proteins upon demand (so called self immolative linkers).  Materials that respond to enzymes, chemical triggers and reductive pH will be discussed with a focus on therapeutics for diabetes.