3次元組織培養における局所環境制御のためのハイドロゲルシステムの開発

开发用于 3D 组织培养中局部环境控制的水凝胶系统

• 批准号: 21F20708
• 负责人: 竹内 昌治
• 金额: $ 0.77万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-28 至 2022-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21F20708/
• 关键词: Nanoparticles; hydrogel; controlled release; DNA; photothermal effect; microfluiddic; cell culture; epithelial cells

The focus of my research was the development of various nanoparticle systems that could be introduced into commercial hydrogels to tune their properties. Together with a collaborator, I developed a method to coat large beads with functional polymers, a study that was published on Colloid and Interface Science Communications. Such a method required a precise control of the particles’ surface, and a second article that describes this surface reaction is currently under preparation. I then used this method to prepare gelatin-coated beads that are responsive to matrix metalloproteinase 9 (MMP-9), an enzyme that plays an important role in various diseases. The plan is to use these beads to develop a MMP-9 biosensor in FY22.Another nanoparticle system that I developed was based on gold nanorods and DNA, for the targeted release of enzymes. Gold nanorods can very efficiently heated using a red laser, and the resulting heath is transferred to the surrounding environment. When double strands of DNA are immobilized on the rods’ surface, the heath causes DNA melting and release of one strand. I confirmed this process using fluorophore-labelled DNA, the next step will be using an enzyme-labelled DNA. Finally, I also developed a liposomes loaded with Ca2+ ions, which could release their cargo when the temperature is above 40 C. An increase of Ca2+ ions can cause physical changes in some hydrogels, for example an increase in stiffness of alginate gels. In order to selectively heath only the liposomes, small (4 nm) gold particles were embedded in their phospholipid bilayer.

我的研究重点是开发各种纳米颗粒系统，这些系统可以引入商业水凝胶中以调节其性能。我与一位合作者一起开发了一种用功能聚合物包覆大珠子的方法，这项研究发表在《胶体与界面科学通讯》上。这种方法需要精确控制颗粒的表面，目前正在编写描述这种表面反应的第二篇文章。然后，我用这种方法制备了明胶涂层的珠子，这些珠子对基质金属蛋白酶9（MMP-9）有反应，MMP-9是一种在各种疾病中起重要作用的酶。计划在2022财年使用这些珠子开发MMP-9生物传感器。我开发的另一种纳米颗粒系统是基于金纳米棒和DNA，用于酶的靶向释放。金纳米棒可以使用红色激光非常有效地加热，产生的热量被转移到周围环境中。当双股DNA固定在杆的表面上时，健康会导致DNA熔化并释放出一股。我使用荧光团标记的DNA证实了这一过程，下一步将使用酶标记的DNA。最后，我还开发了一种负载Ca 2+离子的脂质体，它可以在40 ℃以上释放它们的货物。Ca 2+离子的增加可引起某些水凝胶的物理变化，例如藻酸盐凝胶的刚度增加。为了选择性地仅使脂质体健康，将小（4 nm）金颗粒嵌入其磷脂双层中。