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

PI：Nieh，Mu-Ping提案编号：1433903机构：康涅狄格大学标题：EIGER：分子结构对通过聚合物连接的基于脂质的纳米关节相互作用的影响来自康涅狄格大学的首席研究员Nu-Ping Nieh教授建议遵循他实验室最近的一项发现，他可以自组装脂泡或双层圆盘的“串状”簇。这些结构非常新颖，人们对它们几乎一无所知，因此PI提出了一个迫切的问题，即如何控制“串连”机制，以及它们是否具有感知和控制释放治疗药物的必要性质。如果成功，“串接”NP集群的平台可以用于但不限于两个直接的应用，这是PI长期研究愿景的一部分：单细胞检测和治疗。前者将对食品/水安全方面的公众健康产生重大影响，因为无需训练有素的人员即可在现场进行快速、无仪器和低成本的单一病原体检测，这将极大地惠及居住在偏远地区和无法获得检测仪器的人。后者将为更有效地针对癌症或其他疾病的递送纳米载体的分子设计提供洞察力。PI有致力于本科生和研究生的学生培训的历史。由于样本准备简单，参与该项目的本科生将有进行这项研究的实践经验。此外，这个项目还可以为公众和K-12学生提供很好的纳米技术示范。一个稳定、稳定、稳定的最终成功结果？核糖核酸对单细胞(单一病原体)的检测可能会产生重大影响，因为它成本更低，灵敏度更高。最终，无仪器检测可能是可以实现的，从而允许对传染病进行现场检测。如果这种模板可以被证明是潜在的有用的结合疏水分子，那么它也有潜力作为透气输送载体。PI建议研究几个参数，这些参数可以潜在地控制‘串连’机制，包括NP的曲率，脂类碳氢链的结晶度，由短链脂类引起的缺陷，共聚物的两个末端嵌段的疏水性，以及被包裹的分子(或表面修饰分子)。研究中的脂质混合物将由长链二棕榈酰(di-C16)磷脂酰胆碱(DPPC)和短链二己酰(di-C6)磷脂酰胆碱(DHPC)组成，其中掺杂了略带电荷的长链脂质二棕榈酰磷脂酰甘油(DPPG)，其中稳定的纳米盘和纳米微囊可以自组装。这些初步研究的目的是为如何控制稳定建立一个基线。然后将进行进一步的研究，将疏水部分结合到簇中，以测试它们在潜在应用中的稳定性，这将涉及将疏水分子结合到双层中。

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.