| 研究実績の概要 |
Covalent organic frameworks (COFs) are promising as carriers for drug delivery because of their large drug loading capacity and tunable functionality. However, for practical applications, there is an issue to be addressed; site-selective drug release, because leakage of drugs in non-target tissues leads to side effects. Therefore, in this study, we decided to use proteins as a gate to realize controlled drug release. Specifically, we design a bioadhesive COF (Glue-COF) bearing multiple guanidinium ion for immobilization of proteins. Since there are many types of proteins that undergoes a structural transition in response to biological signals, drug can be released at only target tissues. Calmodulin was chosen as a gate and controlled guest release through the conformational changes of calmodulin by calcium ions (Angew. Chem., Int. Ed. 2021, 60, 8932-8937, selected as a Hot Paper and Front Cover). These experimental results indicate the possibility that protein conformational changes can be used as gates for substance transportation. Many proteins are known to exhibit high binding efficiency to a specific molecule and cause a conformational change upon binding. This achievement is expected to have various applications such as the release of drugs in response to stimuli.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
1: 当初の計画以上に進展している
理由
As planned, bio-adhesive COF (Glue-COF) was synthesized, and its chemical structure was clarified by the various analytic methods. We succeeded in incorporating the protein as a gate to the surface of Glue-COF, which led to the stimuli-responsive guest release via conformational change of protein gate with high selectivity. Apart from this, we also found that Glue-COF can be used to connect vesicles consisting of phospholipid bilayer membranes acting as a channel for substance transfer. This is an unexpected result, showing great potential in the field of drug delivery. Thus, we evaluated our research was more progressed than we planned at the beginning.
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| 今後の研究の推進方策 |
It also has been found that Glue-COF can be used to connect vesicles consisting of phospholipid bilayer membranes. In addition, when the pores of Glue-COF are filled with a dye, which generates singlet oxygen by light irradiation, mass transport is induced between the vesicles in response to light irradiation. For the practical application toward the medical field, we will investigate what kind of substance can be transferred by using different types of fluorescent dyes, drugs, and siRNA, and so on. After that, we will demonstrate whether this technology is suitable for living cells. In this case, Hep3B cells and lipids are expected to be the main research expenses.
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