EAGER: Crosslinked Biodegradable Nanoparticles by Thiol-Ene Miniemulsion Reaction

1019227 Cheng智力优点将生物降解性与纳米结构相结合，产生了具有最小长期毒性和重要生物医学应用的纳米材料。然而，通过简单和强大的协议获得定义明确的可生物降解的纳米材料仍然具有挑战性。本研究的重点是通过硫醇-烯微乳液交联反应合成环境友好的聚合物纳米材料的方法。PI先前发现烯丙基官能化丙交酯（LA）单体在硫醇-烯反应中具有高反应性。一个定义明确的PLA为基础的共聚物与侧链烯丙基进一步获得通过有机催化开环共聚的功能单体与LA;透明的细乳液制备相对较低的表面活性剂浓度。一个关键的问题是含硫醇的细乳液系统是否具有足够的稳定性，以允许良好控制的模板合成。在这项探索性研究中，PI计划使用基于PLA的共聚物与细乳液纳米液滴内的多官能硫醇之间的硫醇-烯反应来合成基于PLA的纳米颗粒。这是一种高风险的方法，因为以前没有探索过。然而，如果成功的话，结果可能会为制造可生物降解的纳米材料带来新的途径。在实验上，通过DLS监测，将研究细乳液反应体系的稳定性，并优化细乳液条件以精确控制所得纳米颗粒。DLS、FT-IR、AFM和TEM将用于表征纳米颗粒。更广泛的影响该研究可能导致对具有不同结构特征的可生物降解纳米颗粒的广泛合成研究，以及对纳米颗粒的降解和递送行为的详细研究。由于这些可生物降解的纳米结构可用于通过纳米封装或缀合来递送抗癌药物，因此最终该项目可能具有社会医疗保健效益。通过硫醇-烯细乳液交联合成纳米颗粒的视频将作为开放源材料在互联网（包括YouTube）上提供，以促进聚合物教育。还将通过面向布法罗和周边学区（公立和私立学校）中学生的“护照STEM”计划进行广泛传播。

1019227Cheng 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).