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

类多肽是小的蛋白质样分子，其在溶液中自组装形成纳米颗粒。类多肽可以高精度合成，并且完全生物相容，从而在治疗和药物递送中具有重要的潜在用途。在这些应用中，基于类多肽的药物载体必须在细胞内有效地递送药物，因此需要详细了解它们与细胞膜的相互作用。这项工作旨在利用被称为脂质体的膜模型来设计特定的类多肽系统与细胞膜的相互作用。这些是溶液中的小亚微米颗粒，其包含具有细胞壁样柔性外膜的内部隔室。 研究人员将通过实验研究单层和多层脂质体的形成和破坏，以设计各种系统，以靶向方式将药物递送到细胞。 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，调查人员致力于通过动手示范向K-12学生开展外联活动。外联的一个重要方面将是使新奥尔良社区学院系统的过程技术学生接触推动化学、石化和制药业务的分子方面。 将在这项工作中开发的特定类别的类多肽包括疏水改性的类多肽或HMP，其通过疏水物插入到双层中与脂质双层相互作用，从而破坏双层以形成HMP+脂质片段或筏。疏水效应表现的显著方面是这些HMP+脂筏重新附着到完整脂质体上以形成额外层的倾向。初步的实验观察表明，有一个片状的缠绕和组装这些筏到脂质体上，导致双层和多层的脂质体。 疏水物在聚合物两亲物如HMP中的连接性带来高密度的插入，导致脂质体破裂成可能完整的双层片段。片段的再附着也是疏水相互作用的一种以前未被认识的表现。因此，对这种现象的基础研究将导致对脂质体上的构建层的控制，并因此导致开发新类别的完全生物相容的聚合物-脂质组装体。使用设计的连接性聚合物两亲物在脂质体和红细胞体上构建双层的潜力具有重要的技术意义。这些概念与含药物的脂质实体与细胞膜和囊泡系统的连接有关。HMPs重塑脂质体的能力是多层自组装的一个新方面，在使用脂质体作为多种药物载体方面具有重要应用。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.