Biodegradable Nanomaterials by Thiol-Ene Miniemulsion Reactions

建议编号：1133737PI：程，冲智能优点聚合物纳米粒(NPs)和纳米胶囊(NCs)在生物医学和其他领域的潜在应用引起了人们的极大兴趣。纳米模板中的受控交联使这些具有三维共价结构的纳米材料的合成成为可能。相应地，合成效率不仅取决于反应或聚合技术，而且取决于模板条件。相对于其他模板方法，基于微乳液的方法通常是简单和环保的，但在对所产生的纳米结构的精确控制方面可能存在不足。特别是，尽管NCS可以很容易地通过微乳液界面交联法获得，但可能会发生严重的界面不稳定，从而产生定义不明确的产品。该项目旨在开发一种最先进的微乳液技术，用于高效、环保地制备定义明确的纳米颗粒和纳米颗粒。该合成策略包括三个主要设计考虑：1)紫外光诱导的硫醇-烯点击化学与透明微乳液相结合，以实现高合成效率；2)通过分散相中聚合物嵌段的选择性交联，最大限度地减少界面不稳定，以对NPs和NCs实施精确的结构控制；以及3)使用环境友好的试剂和反应条件制备可生物降解的纳米材料。在最初的概念验证研究中，利用透明细乳液反应体系的短时间(30分钟)紫外光照射，通过前驱体聚合物(即烯丙基功能化的聚乳酸和聚氧乙烯-b-聚乳酸)的硫醇-烯交联，获得了可生物降解的纳米颗粒和纳米颗粒。通过对每个试验的FTIR分析，确认了几乎完全的反应程度。利用差示扫描量热仪、透射电子显微镜和原子力显微镜对纳米颗粒和纳米颗粒的纳米结构进行了表征。酶降解实验也证明了它们的生物降解性。对这些纳米材料的合成进行了系统的研究，目标是对其纳米尺寸、内部交联结构和功能进行精确控制。通过硫醇-烯功能化策略，将制备各种各样的功能纳米颗粒和纳米碳管，包括那些带有阳离子基团的纳米颗粒和纳米碳管。将优化加工方法和条件，进一步提高合成效率。这些纳米材料的胶体稳定性、降解性和包封性/释放性将被研究。为了进一步评估这些纳米材料作为生物医学载体的可行性，我们将进行体外细胞摄取和细胞毒性研究，并检测siRNA与阳离子NPs和NCS的复合体的转染效率。原则上，除了烯烃功能化的聚合物外，多官能团小分子烯烃也可以在透明的微乳液中通过硫醇-烯反应很容易地转化为纳米材料。本研究结果可进一步为硫醇-烯热诱导细乳液反应以及其他乳液体系中的硫醇-烯反应提供重要的指导。本工作开发的透明细乳液模板有可能应用于其他类型的光诱导反应，以实现高合成效率。广泛影响：该研究计划可能会在材料合成和加工的研究领域带来革命性的影响。由此产生的可生物降解的纳米材料可能会通过帮助改善国民健康和维护环境而为社会带来重大利益。特别是，具有酸不稳定交联性的聚氧化乙烯/聚乳酸为基础的纳米碳管可能是非常有用的支架材料，可用于制备抗癌纳米药物；阳离子纳米粒子和纳米碳管可用于药物和基因的联合输送。本项目的研究成果将促进PIS之间的跨学科合作？在与工业伙伴的合作努力的基础上，我们将在聚合物的生物医学应用方面取得进展，并有可能导致硫代烯微乳液技术的商业化。为了广泛传播聚合物合成技术，将制作关于聚合物制备的视频并在网上播放。将开发一门关于聚合物纳米材料的新研究生课程，以加强纽约州立大学布法罗分校的材料教育和研究。将开展外联活动，促进当地初中生在理工科领域的教育和准备工作。

Proposal Number: 1133737PI: Cheng, Chong Intellectual MeritPolymeric nanoparticles (NPs) and nanocapsules (NCs) have attracted significant interest for potential applications in biomedical and other areas. Controlled cross-linking within nanoscopic templates has allowed the synthesis of these nanomaterials with three-dimensional covalent architectures. Correspondingly, synthetic efficiency depends not only on the reaction or polymerization techniques but also on the template conditions. Relative to other templating approaches, miniemulsion-based methods typically are facile and eco-friendly, but may suffer deficiency in precise control over the resulting nanostructures. Particularly, although NCs can be readily obtained by miniemulsion interfacial cross-linking, dramatic interfacial destabilization may occur to yield ill-defined products. This project is to develop a state-of-art miniemulsion technology for the highly efficient and environmentally friendly preparation of well-defined NPs and NCs. The synthetic strategy incorporates three major design considerations: 1) UV-induced thiol-ene click chemistry is combined with transparent miniemulsions to achieve high synthetic efficiency; 2) interfacial destabilization is minimized by selective cross-linking of polymer blocks in the dispersed phase to exert accurate structural control of NPs and NCs; and 3) biodegradable nanomaterials are produced using environmentally benign reagents and reaction conditions. In the initial proof-of-concept studies, biodegradable NPs and NCs were obtained by thiol-ene cross-linking of precursor polymers, i.e. allyl-functionalized PLA and PEO-b-PLA, using short (30 min) UV irradiation of transparent miniemulsion reaction systems. Nearly complete extent of reaction was confirmed by FTIR analysis for each trial. Well-defined nanostructures of the NPs and NCs were verified by DLS, TEM, and AFM characterizations. Their biodegradability was also proven through enzymatic degradation study. Systematic studies on the synthesis of these nanomaterials are planned towards the goal of exerting accurate control over their nanoscopic dimensions, internal crosslinked structures, and functionalities. A broad variety of functional NPs and NCs, including these with cationic groups, will be prepared via thiol-ene functionalization strategy. The processing method and conditions will be optimized to further improve synthetic efficiency. Colloidal stability, degradation and encapsulation/release behaviors of these nanomaterials will be studied. To further evaluate the viability of these nanomaterials as carriers for biomedical delivery, in vitro cellular uptake and cytotoxicity studies will be conducted, and transfection efficiency of complexes of siRNA with cationic NPs and NCs will be examined. In principle, besides alkene-functionalized polymers, multifunctional small molecule alkenes may also be readily converted into nanomaterials by thiol-ene reactions in transparent miniemulsions. The results from this research could further provide an important guide for thermally-induced thiol-ene miniemulsion reactions, as well as thiol-ene reactions in other emulsion systems. Transparent miniemulsion templates developed in this work potentially may be applied for other types of photoinduced reactions to achieve high synthetic efficiency.Broader Impacts: The research program may bring transformative impacts in the research area of material synthesis and processing. The resulting biodegradable nanomaterials may be utilized to make significant benefits to society by helping to improve national health and maintain environment. Particularly, the PEO/PLA-based NCs with acid-labile cross-linkages may be very useful as scaffolds to create anti-cancer nanomedicines; the cationic NPs and NCs may be employed for the co-delivery of drug and gene. The research findings of this project will promote the interdisciplinary collaboration of the PIs? groups on biomedical applications of polymers, and potentially lead to the commercialization of the thiolene miniemulsion technology based on collaborative efforts with industrial partners. In order to broadly disseminate polymer synthetic technologies, videos on polymer preparation will be created and on-line broadcast. A new graduate course on polymeric nanomaterials will be developed to enhance material education and research at SUNY-Buffalo. Outreach will be conducted to promote the education and preparation of local middle and high school students in science and engineering fields.