| 研究実績の概要 |
In the year of FY2022, the development and optimization of iron(II)-responsive drug release system in vitro was mainly conducted. Several oxime ester models were designed and synthesized. The stability and reactivity towards Fe2+ in aqueous solutions were evaluated. The proposed reaction mechanism and reaction product for the Fe2+-activated release were confirmed by ESI-MS spectra. Fluorescent cyanine dye and tumor-targeting moiety cRGD were synthesized by following the reported work of our research group.
My research also focused on the design and synthesis of novel reaction-based functional fluorescent sensors to detect the diseases-related tiny changes in biological specimens such as pH, and enzymes. Due to the poor water-solubility and easily aggregation of cyanine dyes in aqueous solutions which hamper their biocompatibility in biological application. I am trying to develop the water-soluble Near-infrared pH-responsive cyanine dyes through introduction of several sulfonate groups to the benzoindole moiety of cyanine dyes. The dyes containing two or three anionic groups exhibited better water-solubility even in aqueous solutions without surfactant or organic solvents. Interestingly, I found that the aggregation nanoparticle size of dye in aqueous solutions was changed dependent on pH values which is promising to be used for the improved EPR effect for targeted and specific tumor imaging in vivo models.
Besides, some cell experiments about enzyme-responsive probes for the cooperations with other researcher were conducted in this year.
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| 今後の研究の推進方策 |
For the research theme of Fe2+-triggered drug release, the fluorescent probe containing oxime ester moiety, drug, and tumor-targeting group will be synthesized. The Fe2+-activatable oxime cleavage of probe will be further evaluated. Next, fluorescent turn-on properties of probe based on FTRET effect and drug release will be examined by their UV-vis absorbance and fluorescent spectra. The selectivity and reactivity toward iron(II) over other metal ions, such copper, Zinc, will be evaluated to mimic the conditions in living systems. The length of linker between fluorescent dye and drug will be optimized. Then the drug delivery efficiency will be further optimized in vitro. After achieving the good properties in tube models, the optimized oxime ester-based drug releasing probe will be applied to molecular imaging in the cultured cells and tumor-bearing mice models. By using cRGD as a tumor-targeting moiety which can specifically and strongly bind αvβ3 integrin receptor, the A549 cell line with overexpression levels of cRGD receptor will be chosen for the living cell and in vivo experiments. Finally, tumor inhibition efficiency will be investigated by evaluation of relative tumor volume and weights.
At the same time, my research based on pH-responsive and tumor-targeting NIR cyanine probe will be continue, the in vivo fluorescence imaging of tumor-bearing mice will be conducted in the near future.
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