Photoresponsive self-assembled structures

光响应自组装结构

• 批准号: RGPIN-2019-07142
• 负责人: Murphy, Robert
• 金额: $ 1.75万
• 依托单位: University of Regina
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=716399
• 关键词: Photoresponsive; self; assembled; structures

We are developing amphiphilic organic molecules that respond to light by changing their structure and properties. These light-driven molecular switches (i.e., photoswitches) will be integrated with lipid vesicles to form photoresponsive self-assembled structures. These biocompatible self-assemblies will have potential application in on-demand' drug delivery and theranostics (i.e., therapy and diagnostics). Nanoparticle delivery vehicles offer many advantages over conventional drug formulations. They increase drug solubility, minimize drug degradation, reduce clearance from the body, and enhance therapeutic efficacy. In addition, a delivery vehicle with light-triggered release provides a high level of spatial and temporal control. As a result, a higher local concentration of therapeutics can be dispensed, reducing the overall injected dose and systemic toxicity. Further, photoresponsive delivery vehicles with reversible photoswitches allow for repeated on-demand' dosing from a single administration. Currently, the main challenge facing photoresponsive lipid vesicles as drug delivery systems is the lack of control over the release of hydrophobic therapeutic molecules from the lipid bilayer or hydrophilic molecules from the aqueous core. In addition, most photoswitches rely on high-energy UV light for activity. This dependence hinders the use of photoswitches in biomedical applications because UV light can be damaging to endogenous molecules and has relatively poor tissue penetration, which limits its use to organs that can be directly reached by endoscopic techniques. Consequently, the proposed research program will address these issues. First, we will prepare reversible, amphiphilic photoswitches that undergo a large change in hydrophobicity (i.e., a change in solubility) when irradiated with visible or near infrared (NIR) light. Second, we will examine the effect of photoswitch inclusion and isomerization (i.e., activity) on lipid bilayer mechanics. Namely, we will identify lipid vesicle formulations that undergo large changes in membrane fluidity and thickness upon irradiation with visible or NIR light. Significant photoinduced changes in lipid bilayer mechanics should trigger the formation of pores and enhance membrane permeability. Third, we will perform permeation assays to evaluate the effect of photoswitch activity on the delivery of therapeutics from these vesicle formulations. Overall, we will produce photoresponsive, biocompatible self-assemblies with application in drug delivery and theranostics. These objectives represent a systematic approach for achieving photocontrol in lipid-based self-assembled structures. This approach will lead to patentable technologies and benefit public health.

我们正在开发两亲性有机分子，通过改变它们的结构和性质来响应光。这些光驱动的分子开关（即，光开关）将与脂质囊泡整合以形成光响应自组装结构。这些生物相容性自组装体将在按需药物递送和治疗诊断学（即，治疗和诊断）。纳米颗粒递送载体提供了许多优于常规药物制剂的优点。它们增加药物溶解度，使药物降解最小化，减少从身体的清除，并增强治疗功效。此外，具有光触发释放的递送载体提供了高水平的空间和时间控制。因此，可以分配更高的局部浓度的治疗剂，从而降低总注射剂量和全身毒性。此外，具有可逆光开关的光响应性递送载体允许从单次施用重复按需给药。目前，光响应脂质囊泡作为药物递送系统所面临的主要挑战是缺乏对疏水性治疗分子从脂质双层或亲水性分子从水性核心的释放的控制。此外，大多数光开关依赖于高能紫外光进行活动。这种依赖性阻碍了光开关在生物医学应用中的使用，因为UV光可能对内源性分子造成损害，并且具有相对较差的组织穿透性，这限制了其对可以通过内窥镜技术直接到达的器官的使用。因此，拟议的研究计划将解决这些问题。首先，我们将制备可逆的两亲性光开关，其经历疏水性的大变化（即，溶解度的变化）。其次，我们将研究光开关包含和异构化的影响（即，活性）对脂质双层力学的影响。也就是说，我们将鉴定在用可见光或NIR光照射时膜流动性和厚度发生大变化的脂质囊泡制剂。脂质双层力学的显著光诱导变化应触发孔的形成并增强膜渗透性。第三，我们将进行渗透试验，以评估光开关活性对这些囊泡制剂递送治疗剂的影响。总的来说，我们将产生光响应，生物相容性的自组装与药物输送和治疗诊断的应用。这些目标代表了一个系统的方法，实现光控在基于脂质的自组装结构。这种方法将导致可申请专利的技术，并有利于公众健康。