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

点击翻译按钮获取中文摘要

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.