| 研究実績の概要 |
In the fiscal year 2019, we utilize the 1,3-dipolar cycloaddition reaction between phenyl azide and acrolein for cancer treatment. Previously we found that phenyl azide could react with acrolein to give triazoline, which could further transform into the diazo derivative. Herein by attaching the anticancer drug to the phenyl azide through carbamate linker, we demonstrated the feasibility of phenyl azide-acrolein reaction to release the anticancer drug only in cancer cells.
Based on the observation that acrolein is produced by cancer cells in significant amounts, we hypothesized that anticancer drug-conjugated phenyl azide could selectively react with acrolein in cancer cells. Thus, we added the anticancer drug-conjugated phenyl azide into various cell lines. Our findings indicated that the phenyl azide reacts with acrolein produced by cancer cells. Thus, the drug can be released and shows toxicity only in cancer cells, but not with the healthy cells. This method might be useful for cancer treatment not only in live cells but also in living animals.
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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
We have successfully utilized a simple click reaction between phenyl azide and acrolein to release cancer drugs on the specific target selectively. Moreover, we also found that a bulky phenyl azide could react with acrolein faster than the regular phenyl azide.
We were able to show that drug conjugated-phenyl azide rapidly and efficiently destroys the cancer cells, but not the healthy cells.
We also performed a preliminary experiment with cancer mouse models. This new method has the potential to treat cancer without showing any side effects.
This organic synthetic chemistry-based method could be applied widely to deliver and release specific molecules only at cancer cells without affecting the healthy cells.
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| 今後の研究の推進方策 |
This research utilizes the in vivo click reaction of endogenous acrolein as the crucial reaction. In the fiscal year 2019, we achieved an excellent outcome. We observed that the drug-conjugated phenyl azide is non-toxic against healthy cells. However, the drug-conjugated phenyl azide could react with endogenous acrolein, which significantly overexpressed in cancer cells, to release and activate the anticancer drug in cancer cells. In other words, the azide-acrolein “click-to-release" reaction will selectively occur only at the cancer cells to activate the anticancer drug only at the target area and leave the healthy cells intact.
Based on these results, in the fiscal year 2020, the research will focus on the application of this new method in living animals. The preliminary results of animal experiments have shown promising results. Thus, xenograft mouse will be prepared, and the selectivity and effectiveness of this method for cancer treatment will be examined by comparing it with various control compounds.
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