Adaptive Artificial Receptors for Biomimetic Functions

仿生功能的自适应人工受体

• 批准号: MR/X023303/1
• 负责人: Sarah Pike
• 金额: $ 75.7万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX023303%2F1
• 关键词: Adaptive; Artificial; Receptors; Biomimetic; Functions

In recent years, chemists have developed efficient methods for making molecular containers from simple building blocks. These molecular containers are of great interest as chemists have shown that the hollow cavity within their centre can be used to capture a range of guest molecules on the inside the container. Chemists often choose to capture guest molecules with biological relevance as these systems then have the potential to then be used for medical applications; for example to treat diseases within our bodies. These molecular containers are able to do this as they selectively capture the anticancer molecule within the central cavity of the molecular container, which protects them as they move around the body and, then, releases them at the site of the disease (i.e. a tumour). However, one of the major drawbacks of many existing molecular containers is that because they are made from rigid artificial building blocks, these inflexible molecular containers are unable to display responsive behaviour. As a result, the rigid molecules containers, unlike biological systems, are not able to adapt to the changes in environment and, instead of being able to treat a disease at a specific site within our bodies, they will interact with different molecules within our bodies and lose their ability to effectively treat the disease at its source. Therefore, in order to make full use of the potential of these molecular containers for medical applications within our bodies (e.g., anticancer treatments) we need to make sure that they can interact with only the desired guest molecule (e.g., a drug molecule) and not with all the other undesired molecules that exist within our bodies. Moreover, many existing molecular containers cannot be dissolved in water and, hence, are not compatible for use within our bodies.The proposed research addresses these problems associated with existing rigid molecular containers and describes the development of a new type of molecular container that uses flexible building blocks made from biologically inspired components that are water compatible and, hence, can potentially be used in our bodies. These bioinspired molecular containers have specific sites incorporated into their central cavity which allows them to be able to selectively interact with the one desired guest molecule from a large mixture of guest molecules. The ability of these flexible molecular containers to selectively interact with one molecule in a complex mixture of molecules is inspired by the "lock-and-key" mechanisms used by nature. Moreover, the flexible nature of the biologically inspired building blocks also allows these new molecular containers to undergo controlled changes in their shape so that they can completely break apart in order to release the guest molecule from the central cavity in a controlled manner when desired. This responsive behaviour of the molecular container, for the controlled capture and release of one specific and desired guest molecule (for example, anti-cancer drug molecule) even in the presence of large numbers of other undesired guest molecules, means that they have the potential to adapt to the complicated environments found within our bodies. As a result of this responsive behaviour, these new flexible molecular containers have the potential to be used for biomedical applications e.g., capturing an anticancer drug molecule, transporting it to the site of tumour within our bodies and then releasing the anticancer drug at the tumour site in order to treat the disease in a more efficient manner than current anti-cancer treatments. The development of these new molecular containers, which contain flexible biological building blocks, that are able to adapt to interact with one desired guest molecule from a complex mixture, have a clear advantage over many existing ones as they have the striking potential to carry out medical applications within our bodies, for example delivering a drug at a tumour.

近年来，化学家们已经开发出了用简单的积木制造分子容器的有效方法。这些分子容器引起了极大的兴趣，因为化学家们已经证明，它们中心的空心腔可以用来捕获容器内部的一系列客体分子。化学家通常选择捕获具有生物学相关性的客体分子，因为这些系统随后具有用于医学应用的潜力；比如治疗我们体内的疾病。这些分子容器能够做到这一点，因为它们有选择性地捕获分子容器中心腔内的抗癌分子，当抗癌分子在体内移动时保护它们，然后在疾病部位（即肿瘤）释放它们。然而，许多现有分子容器的主要缺点之一是，因为它们是由刚性的人造构件制成的，这些不灵活的分子容器无法显示响应行为。因此，与生物系统不同，刚性分子容器不能适应环境的变化，它们不能在我们体内的特定部位治疗疾病，而是会与我们体内的不同分子相互作用，从而失去在源头有效治疗疾病的能力。因此，为了充分利用这些分子容器在我们体内的医疗应用（例如抗癌治疗）的潜力，我们需要确保它们只能与所需的客体分子（例如药物分子）相互作用，而不能与我们体内存在的所有其他不需要的分子相互作用。此外，许多现有的分子容器不能溶于水，因此不适合在我们体内使用。拟议的研究解决了与现有刚性分子容器相关的这些问题，并描述了一种新型分子容器的开发，这种容器使用由生物启发的组件制成的柔性构建块，这些组件与水兼容，因此有可能用于我们的身体。这些受生物启发的分子容器在其中心腔中包含特定的位点，这使得它们能够从大量的客体分子混合物中选择性地与一个所需的客体分子相互作用。这些灵活的分子容器选择性地与复杂分子混合物中的一个分子相互作用的能力是受到自然界使用的“锁与钥匙”机制的启发。此外，受生物启发的构建块的灵活性也允许这些新的分子容器在其形状上经历可控的变化，以便它们可以完全分解，以便在需要时以可控的方式从中心腔中释放客体分子。分子容器的这种响应性行为，即使在存在大量其他不需要的客体分子的情况下，也能控制捕获和释放一种特定的和所需的客体分子（例如抗癌药物分子），这意味着它们有可能适应我们体内发现的复杂环境。由于这种反应性行为，这些新的柔性分子容器具有用于生物医学应用的潜力，例如，捕获抗癌药物分子，将其运送到我们体内的肿瘤部位，然后在肿瘤部位释放抗癌药物，以便以比目前抗癌治疗更有效的方式治疗疾病。这些新型分子容器的开发，包含灵活的生物构建块，能够适应与复杂混合物中的一个所需的客体分子相互作用，与许多现有的分子相比，具有明显的优势，因为它们具有在我们体内进行医学应用的惊人潜力，例如在肿瘤上输送药物。