Collaborative Research: The Use of Amphiphilic Polypeptoids to Connect Nanoparticle containing Lipid Rafts onto Liposomes and Erythrosomes through Self-Assembly.

合作研究：使用两亲性多肽通过自组装将含有脂筏的纳米颗粒连接到脂质体和红细胞体上。

• 批准号: 1805608
• 负责人: Vijay John
• 金额: $ 25万
• 依托单位: Tulane University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1805608&HistoricalAwards=false
• 关键词: Collaborative; Research; Use; Amphiphilic; Polypeptoids

Polypeptoids are small protein-like molecules that self-assemble to form nanoparticles in solution. Polypeptoids can be synthesized with a high degree of precision and are entirely biocompatible, leading to significant potential uses in therapeutics and drug delivery. In such applications, the polypeptoid based drug carriers must effectively deliver the drug within the cell, thus requiring a detailed understanding of their interactions with cell membranes. This work seeks to engineer the interactions of specific polypeptoid systems with cell membranes using membrane models known as liposomes. These are small submicron particles in solution that contain an interior compartment with a cell-wall-like flexible external membrane. The investigators will experimentally study the formation and disruption of single and multi-layer liposomes to engineer a variety of systems to deliver drugs to cells in a targeted way. As part of this work, undergraduate and graduate students will be trained in the use of sophisticated experimental tools. In addition, the investigators are committed to outreach activities to K-12 students through hands-on demonstrations. A strong aspect of the outreach will be to expose process technology students in the New Orleans Community College system to the molecular aspects that drive chemical, petrochemical, and pharmaceutical operations. The specific class of polypeptoids that will be developed in this work include the hydrophobically modified polypeptoids or HMPs, which interact with the lipid bilayers through hydrophobe insertion into the bilayers, and thus disrupt the bilayer to form HMP+lipid fragments or rafts. The remarkable aspect of the manifestation of the hydrophobic effect is the propensity of these HMP+lipid rafts to reattach onto intact liposomes to form additional layers. Preliminary experimental observations indicate that there is a sheet-like winding and assembly of these rafts onto liposomes leading to double and multiple layers on liposomes. The connectivity of hydrophobes in a polymeric amphiphile such as HMP brings about a high density of insertions leading to rupture of liposomes into perhaps intact bilayer fragments. The reattachment of fragments is also a previously unrecognized manifestation of the hydrophobic interaction. Thus, a fundamental study of this phenomenon will lead to control over building layers onto liposomes and therefore lead to the development of new classes of fully biocompatible polymer-lipid assemblies. The potential to build bilayers onto liposomes and erythrosomes using a designed connective polymeric amphiphile has significant technical implications. These concepts have relevance to the attachment of drug-containing lipid entities to cell membranes and to vesicle systems. The ability of HMPs to remodel liposomes is a novel aspect of multilayer self-assembly with significant applications to using liposomes as multiple drug carriers.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

多肽是一种类似蛋白质的小分子，在溶液中自组装形成纳米颗粒。多肽类化合物可以高度精确地合成，并且具有完全的生物相容性，在治疗学和药物输送方面具有重要的潜在用途。在这种应用中，基于多肽的药物载体必须有效地将药物输送到细胞内，因此需要详细了解它们与细胞膜的相互作用。这项工作试图利用被称为脂质体的膜模型来设计特定多肽系统与细胞膜的相互作用。这些是溶液中的亚微米小颗粒，其中包含一个内部隔室，内部隔间有一个像细胞壁一样的柔性外膜。研究人员将对单层和多层脂质体的形成和破坏进行实验研究，以设计各种系统，以有针对性的方式将药物输送到细胞。作为这项工作的一部分，本科生和研究生将接受使用复杂实验工具的培训。此外，调查人员还致力于通过亲身示范向K-12学生开展外联活动。外展的一个重要方面将是让新奥尔良社区学院系统的过程技术专业的学生接触推动化学、石化和制药运营的分子方面。在这项工作中将开发的特定类型的多肽包括疏水修饰的多肽或HMPs，它们通过疏水插入到双层中与脂双层相互作用，从而破坏双层形成HMP+脂类碎片或浮筏。疏水效应的显著表现是，这些HMP+脂筏倾向于重新附着在完整的脂质体上，形成额外的层。初步的实验观察表明，这些浮筏以片状缠绕和组装在脂质体上，从而在脂质体上形成双层和多层。疏水分子在聚合物两亲分子(如HMP)中的连接性导致高密度的插入，导致脂质体破裂成可能完整的双层碎片。片段的重新附着也是疏水相互作用的一种以前未被认识的表现形式。因此，对这一现象的基础研究将导致对在脂质体上建立层的控制，从而导致新的类完全生物相容的聚合物-脂质组装体的发展。使用设计的连接聚合物两亲物在脂质体和红体上构建双层的可能性具有重要的技术意义。这些概念与含药脂实体与细胞膜和囊泡系统的附着有关。HMPs重塑脂质体的能力是多层自组装的一个新方面，在将脂质体用作多个药物载体方面具有重要应用。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。