EAGER: The Effects of Molecular Architectures on Lipid-Based Nanoparticulate Interaction through Polymer Linkers

项目编号：1433903机构：康涅狄格大学题目：热切：分子结构对通过聚合物连接的基于脂质的纳米颗粒相互作用的影响首席研究员（PI），来自康涅狄格大学的Mu-Ping Nieh教授正在提议按照他实验室最近的一项发现，他可以自组装脂质囊泡或双层磁盘的“弦”簇。这些结构相当新颖，几乎对它们一无所知，因此PI提出了一个EAGER来确定如何控制“串”机制，以及它们是否具有感知和控制释放治疗药物的必要特性。如果成功，“串”NP集群平台可以用于（但不限于）PI长期研究愿景的两个直接应用：单细胞检测和治疗递送。前者将对食品/水安全方面的公共卫生产生重大影响，因为无需经过培训的人员即可在服务点进行快速、无仪器和低成本的单一病原体检测，这将极大地惠及生活在偏远地区且无法获得检测仪器的人们。后者将为更有效地靶向癌症或其他疾病的递送纳米载体的分子设计提供见解。PI一直致力于本科生和研究生的学生培训。由于样品制备的简单性，参与该项目的本科生将有实践经验来进行这项研究。此外，这个项目可以为公众和K-12学生提供很好的纳米技术示范。一个最终成功的结果是稳定的？NPs可能对单细胞（单一病原体）检测产生重大影响，因为成本更低，灵敏度更高。最终，可以实现无仪器检测，从而实现对传染病的现场服务传感。如果这个模板可以被证明对疏水分子的结合有潜在的用处，那么它也有可能成为治疗性的递送载体。PI建议研究几个可能控制“串”机制的参数，包括NP的曲率，脂质烃链的结晶度，短链脂质引起的缺陷，共聚物的两个末端块的疏水性，以及被捕获的分子（或表面修饰的分子）。研究中的脂质混合物将由长链双棕榈酰（di-C16）磷脂酰胆碱（DPPC）和短链二己醇（di-C6）磷脂酰胆碱（DHPC）组成，DHPC掺杂一种稍带电荷的长链脂质，双棕榈酰磷脂酰甘油（DPPG），其中稳定的纳米圆盘和纳米囊泡可以自组装。这些初步研究的目的是为如何控制稳定性建立一个基线。接下来将进一步研究将疏水分子掺入到聚类中，以测试其稳定性，以用于将疏水分子掺入双分子层的潜在应用。

PI: Nieh, Mu-Ping Proposal Number: 1433903Institution: University of Connecticut Title: EAGER: The Effects of Molecular Architectures on Lipid-Based Nanoparticulate Interaction through Polymer LinkersThe Principal Investigator (PI), Professor Mu-Ping Nieh from the University of Connecticut is proposing to follow a recent discovery in his laboratory that he can self-assemble "stringed" clusters of lipid vesicles or bilayer disks. These structures are quite novel and almost nothing is known about them, so the PI proposes an EAGER to determine how to control the "stringing" mechanism and whether they have the necessary properties for sensing and controlled-release of therapeutics for delivery. If successful, the platform of "stringed" NP clusters can be used for, but not limited to, two immediate applications that is part of the PI's long-range research vision: single-cell detection and theranostic delivery. The former will significantly impact the public health in food/water safety since rapid and instrument-free and low-cost single-pathogen detection can be performed service-at-point without trained personnel, greatly benefiting people who live in a remote area and have no access to testing instruments. The latter will provide insight to the molecular design of delivery nanocarriers to target cancers or other diseases more effectively. The PI has a history of being committed to student training for both undergraduates and graduates. Due to the simplicity of the sample preparation, undergraduates involved in the project will have hands-on experience in conducting this research. Moreover, this project can provide good demonstrations of nanotechnology for the public and K-12 students. An eventual successful outcome of stable ?stringed? NPs could have significant impact on single-cell (single-pathogen) detection because of lower costs and higher sensitivity attainable. Ultimately, instrument-free detection may be achievable, allowing for service-at-point sensing for infectious diseases. If this template can be shown to be potentially useful for incorporation of hydrophobic molecules, then it also has potential as theranostic delivery carriers.The PI proposes to investigate several parameters, which can potentially control the 'stringing' mechanism, including the NP's curvature, the crystallinity of the lipid hydrocarbon chains, the defects induced by the short-chain lipid, the hydrophobicity of two end blocks of the copolymer, and the entrapped molecules (or surface-modified molecules). The lipid mixture in study will be composed of long-chain dipalmitoyl (di-C16) phosphatidylcholine (DPPC) and short-chain dihexanoyl (di-C6) phosphatidylcholine (DHPC) doped with a slightly charged long-chain lipid, dipalmitoyl phosphatidylglycerol (DPPG) where stable nanodiscs and nanovesicles can be self-assembled. The objective of these initial studies is to establish a baseline for how to control stability. Further studies will then be done on the incorporation of hydrophobic moieties into the clusters to test their stability for potential applications that will involve the incorporation of hydrophobic molecules into the bilayer.