| 研究課題/領域番号 |
22K20524
|
|---|
| 研究機関 | 北海道大学 |
|---|
研究代表者 |
|
|---|
| 研究期間 (年度) |
2022-08-31 – 2024-03-31
|
| キーワード | Drug delivery / Nanoparticle / Raman spectroscopy / SERS / Single-cell endoscopy / SN-38 |
|---|
| 研究実績の概要 |
In AY2022, we focused on 1) functionalizing nanoprodrugs and 2) developed the method based on Raman spectroscopy for intracellularly label-free analysis of nanoprodrugs dynamics. The surface of SN-38 nanoprodrugs was decorated with biotin-modified liposomal membranes to enhance the internalization of cancer cells and target specific cellular compartments. For the analysis of intracellular drug dynamics based on single-cell SERS endoscopy, we successfully coated silver nanowire (AgNW) probes of the endoscopy system with ZIF-8 metal-organic framework, enabling the selective detection of molecules based on their molecular sizes and hydrophobicity. The developed method is able to detect the conversion of irinotecan prodrug into SN-38 active drug molecule (Advanced optical materials, 2023 accepted).
|
| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
Most of the research objectives, including the development of SN-38-based DDS and an approach for intracellular dynamic studies, are completed during the first year of implementation. The functionalization of SERS endoscopy probe with ZIF-8 allows the selective detection of drug molecules and its metabolite in the highly complex intracellular environment, which is extremely challenging. We are now progressing to investigating the nanoprodrugs intracellularly based on the successfully developed approach.
|
| 今後の研究の推進方策 |
For AY2023, ZIF-8 modified AgNW single-cell SERS endoscopy developed in AY2022 will be utilized to study SN-38 nanoprodrugs intracellular dynamics. After the SN-38 nanoprodrugs are administrated to cancer cells, their internalization and drug molecule dissolution from nanoparticles will be monitored by fluorescent and Raman spectroscopy techniques. Then, using SERS endoscopy, the conversion of SN-38 prodrug will be monitored at the specified intracellular location over time. After a clear knowledge of the intracellular dynamics of SN-38 nanoprodrugs is obtained, the project will investigate the dynamics of DDS in 3D tumor models.
|
