EAGER: Crosslinked Biodegradable Nanoparticles by Thiol-Ene Miniemulsion Reaction

1019227 Cheng Intellectual Merit Integrating biodegradability with nanostructures has generated nanomaterials with minimized long-term toxicity and important biomedical applications. However, it remains challenging to obtain well-defined biodegradable nanomaterials through simple and robust protocols. This research is focused on a methodology for the synthesis of environmentally benign polymeric nanomaterials via thiol-ene miniemulsion-crosslinking reactions. The PI previously found high reactivity of an allyl-functionalized lactide (LA) monomer in thiol-ene reactions. A well-defined PLA-based copolymer with pendent allyl groups was further obtained by organo-catalyzed ring-opening copolymerization of the functional monomer with LA; transparent miniemulsions were prepared with relatively low surfactant concentrations. A critical question is whether thiol-containing miniemulsion systems have sufficient stability to allow well-controlled templating synthesis. In this exploratory investigation, the PI plans to synthesize PLA-based nanoparticles using the thiol-ene reaction between the PLA-based copolymer and multifunctional thiols within miniemulsion nanodroplets. This is a high-risk approach because it has not been previously explored. However, if successful, results could lead to a new avenue for making biodegradable nanaomaterials. Experimentally, monitored by DLS, stability of the miniemulsion reaction systems will be investigated, and miniemulsion conditions will be optimized to exert precise control over the resulting nanoparticles. DLS, FT-IR, AFM, and TEM will be utilized to characterize the nanoparticles. Broader Impacts The research could lead to extensive synthetic studies of biodegradable nanoparticles with different structural features, as well as detailed investigations of degradation and delivery behaviors of the nanoparticles. Since these biodegradable nanostructures may be used to deliver anti-cancer drugs through nanoencapsulation or conjugation, eventually this project may have societal health-care benefits. A video on nanoparticle synthesis by thiol-ene miniemulsion crosslinking will be prepared as open source material available on the internet (including YouTube) to promote polymer education. Broad dissemination will also be through the 'Passport STEM' program for middle and high school students from Buffalo and surrounding school districts (both public and private schools).