Development of stabilized environmentally sensitive polymeric nanoparticles

稳定环境敏感聚合物纳米粒子的开发

• 批准号: RGPIN-2016-06059
• 负责人: Xing, Malcolm
• 金额: $ 3.13万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=688617
• 关键词: Development; stabilized; environmentally; sensitive; polymeric

Research Problem: Nanoparticles have been extensively explored as carriers to deliver hydrophobic molecules to targeted locations. Hydrophobic molecules do not disperse easily in water and can aggregate, thereby compromising their efficacy. Nanoparticles overcome this challenge by offering a hydrophobic core for hydrophobic payloads, while providing a hydrophilic shell that promotes free dispersion in aqueous solution. Nanoparticles offer the additional benefit to improve payload stability by encapsulating cargos to avoid adverse contact with destabilizing agents before their destination. Recently, progress has been made in developing environmentally sensitive nanoparticles that release their payloads in response to environmental stimuli, which can be either chemical (pH, redox) or physical (temperature, light). Improving the stability and loading efficiency of nanoparticles is a key consideration for a variety of applications. ***Proposed Research: My work is aimed at developing synthetic polymeric nanoparticles that are environmentally sensitive. They remain stable until they are exposed to an environment characterized by low pH, a high reducing potential or a temperature change. These nanoparticles will have potential applications as carriers of bioactive agents to treat diseases or to monitor biological processes as a biosensor.***The goal of the proposed program is to design biopolymers for stabilized nanoparticles with environmental sensitivities. Polymeric nanoparticles will be synthesized with a hydrophobic core and a hydrophilic shell. Redox, pH, and temperature sensitivities will be introduced into the polymers. The rationale is that the nanoparticles can be designed to efficiently release their cargos upon exposure to one or several of these stimuli in a pre-programmed manner. For example, pH and redox sensitivities can facilitate intracellular delivery of cargos due to the low pH value and high level of reducing agents in the intracellular environment. In addition, temperature change can lead to a morphology change of nanoparticles that can promote cargo release. The proposed research will also improve the stability of nanoparticles by studying different crosslinking methods and comparing their effects on stability and payload release. In order to study the effects of hydrophobicity on encapsulation, we will study different hydrophobic molecular chains and assess the resulting loading efficiency. ***Expected Outcome: The research program will optimize the structure and performance of polymeric nanoparticles as carriers of chemical agents, and will also advance our knowledge of functional polymers with environmental sensitivities. This research has the potential to promote the growth of the Canadian Nanomaterials Industry by developing a wealth of new materials. The proposed program will provide cutting edge training for HQP at different levels.**

研究问题：纳米颗粒作为载体被广泛探索，以将疏水分子传递到目标位置。疏水性分子不容易分散在水中，并且可以聚集，从而损害其功效。纳米颗粒通过为疏水有效载荷提供疏水核，同时提供促进在水溶液中自由分散的亲水壳来克服这一挑战。纳米颗粒提供了额外的好处，通过封装货物，以避免在其目的地之前与不稳定剂的不利接触，提高有效载荷的稳定性。最近，在开发环境敏感的纳米颗粒方面取得了进展，这些纳米颗粒响应于环境刺激而释放其有效载荷，这些环境刺激可以是化学的（pH、氧化还原）或物理的（温度、光）。 提高纳米颗粒的稳定性和负载效率是各种应用的关键考虑因素。* 建议的研究：我的工作旨在开发对环境敏感的合成聚合物纳米颗粒。它们在暴露于低pH值、高还原电位或温度变化的环境之前保持稳定。这些纳米颗粒将具有潜在的应用，作为生物活性剂的载体来治疗疾病或作为生物传感器来监测生物过程。该计划的目标是设计具有环境敏感性的稳定纳米颗粒的生物聚合物。聚合物纳米颗粒将被合成为具有疏水核和亲水壳。氧化还原，pH和温度敏感性将被引入到聚合物中。基本原理是纳米颗粒可以被设计成在以预编程的方式暴露于这些刺激中的一种或多种时有效地释放它们的货物。 例如，由于细胞内环境中的低pH值和高水平的还原剂，pH和氧化还原敏感性可以促进货物的细胞内递送。此外，温度变化可导致纳米颗粒的形态变化，这可促进货物释放。拟议的研究还将通过研究不同的交联方法并比较它们对稳定性和有效载荷释放的影响来提高纳米颗粒的稳定性。为了研究疏水性对包封的影响，我们将研究不同的疏水分子链并评估所得的装载效率。* 预期结果：该研究计划将优化聚合物纳米颗粒作为化学试剂载体的结构和性能，并将提高我们对环境敏感性功能聚合物的认识。这项研究有可能通过开发丰富的新材料来促进加拿大纳米材料行业的发展。 拟议的计划将为不同级别的HQP提供尖端培训。**