表面诱导自组装在生物分析检测方面的应用

Surface-induced self-assembly is a new strategy, which can make a molecule self-assemble on the specific surface at the concentration below its minimal self-assembling concentration in its solution due to the interaction between the molecule and surface. This strategy is able to make the self-assembled molecules specifically enrich on the surface that can specially realize the function of self-assembled nanostructures on the surface. First, we plan to make some fluorescent probes produced after the enzyme catalysis enrich on the surface with opposite electric charge through this method. The fluorescent signal on the surface is greatly enhanced, which realize the analysis of enzyme in the complex samples. Secondly, we will rational design and synthesize the fluorescent probes according to the certain receptors on the surface of cancer cells or bacteria. They may especially self-assemble and enrich on the surface of cancer cells or bacteria by surface-induced self-assembly, leading to the great increase of their concentration and fluorescent intensity on the surface. Therefore, these probes can be used for the specific detection of cancer cells or bacteria in vivo and in vitro. Based on the good previous research results and the study on the self-assembly of peptides for years, our plan will not only greatly enrich the contents of the research in the field of supramolecular self-assembly, but also provide a new strategy for practical applications of fluorescent probes.

表面诱导自组装技术是指借助于表面对自组装分子的相互作用力，在低于溶液中最低组装浓度的条件下实现分子在表面上自组装的一种新技术。该技术可使自组装分子在表面上特异性的富集，从而能特异性地实现自组装纳米结构在该表面上的功能。本研究计划第一部分是拟借助于该技术实现酶切之后生成的荧光探针分子在带相反电荷的表面上的富集，通过采用环境响应荧光基团或聚集诱导发光荧光分子可实现该表面上荧光的大大增强，从而实现复杂样品中酶的分析检测。第二部分是拟通过合理设计针对癌细胞或细菌表面特定受体的靶向荧光探针分子，实现自组装荧光探针分子在癌细胞或细菌表面的特异性组装和富集，从而大大提高该分子在目标表面的浓度以及荧光强度，用于体内外癌细胞或细菌的特异性检测或抑制。本研究计划基于良好的前期结果以及多年在自组装多肽研究领域的基础，将极大丰富超分子自组装研究领域的内容同时为荧光探针的实际应用提供了一种新策略。

本研究计划拟通过“表面诱导自组装技术”在各类生物表面例如细胞和细菌等表面构建小分子多肽自组装体，用于探索表面诱导自组装技术在细菌检测和组织工程等领域的应用。在2017-2020年间，项目负责人带领研究团队按照原定计划逐步合成了一系列新型的荧光分子探针，利用表面诱导自组装技术将分子探针应用于正常癌细胞和衰老癌细胞的检测和杀伤；利用表面诱导多肽自组装技术能在癌症原位形成新型纳米药物的策略，设计和制备了一系列新型的多肽纳米药物，并利用多种癌细胞和小鼠肿瘤模型初步探索了这些新型纳米药物的疗效。我们的科研工作为新型抗肿瘤纳米药物的研发提供新的思路和策略。项目执行期间一共发表了标注该基金项目的SCI收录论文12篇，申请中国发明专利4项，获得授权中国发明专利4项，培养了自组装多肽研究方面的多名优秀人才，包括5名博士生，2名硕士生。其中有3名博士生毕业后继续从事科研工作，有1名硕士继续去国外攻读博士学位。2019年获得天津市自然科学一等奖（第九完成人）。

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