UC San Diego

Biological redox molecules play essential regulatory roles in diverse cellular processes. In particular, abnormal levels of redox signaling molecules are related to the progression of several diseases. Therefore, redox-responsive polymeric nanomaterials appear as competent candidates for disease-targeting drug delivery systems. In the past decades, considerable works have been done to develop polymeric nanomaterials showing controlled release in response to reactive oxygen species, glutathione or both. To further advance this research field, two new redox-responsive polymeric nanomaterials are described in this dissertation. In chapter 1, hydrogen peroxide-responsive polycaprolactone nanoparticles are reported. By exploiting an intramolecular cyclization strategy, polycaprolactone that contains pendant arylboronic ester motifs shows fast hydrogen peroxide-induced degradation. Nanoparticles formulated from this polycaprolactone exhibit high sensitivity to disease relevant levels of hydrogen peroxide. In chapter 2, a hydrogen sulfide-responsive nanogel is introduced. Cholesteryl groups were conjugated on dextran via hydrogen sulfide-responsive linkers to yield amphiphilic polysaccharides that can self-assemble to form nanogels in aqueous solutions. This work presents the first hydrogen sulfide-responsive nanogel that shows hydrogen sulfide-induced swelling behavior and controlled payload release.