Label-free intracellular dynamics investigation of carrier-free nanoparticle-based drug delivery systems
| Project/Area Number |
22K20524
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0501:Physical chemistry, functional solid state chemistry, organic chemistry, polymers, organic materials, biomolecular chemistry, and related fields
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2022-08-31 – 2024-03-31
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| Project Status |
Granted (Fiscal Year 2022)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | Drug delivery / Nanoparticle / Raman spectroscopy / SERS / Single-cell endoscopy / SN-38 / Drug delivery systems / Single cell endoscopy / Nanoparticles |
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| Outline of Research at the Start |
Probing the intracellular metabolism of the newly established nanomedicine is crucial for assessing the efficiency of the drug delivery systems. In this work, we aim to be the first to elucidate the intracellular metabolism of SN-38 anticancer nanoprodrugs based on the single cells SERS endoscopy technique. An overall understanding of the intracellular particle degradation, drug molecules diffusion/accumulation, as well as their interaction with biomolecular targets, is expected to pave the way for the further development of advanced drug delivery strategies.
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| Outline of Annual Research Achievements |
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).
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
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.
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| Strategy for Future Research Activity |
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.
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Report
(1 results)
Research Products
(9 results)
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[Journal Article] Selective Detection of Intracellular Drug Metabolism by Metal-Organic Framework- Coated Plasmonic Nanowire2023
Author(s)
Qiang Zhang, Taku Murasugi, Kotomi Watanabe, Han Wen, Ya Tian, Monica Ricci, Susana Rocha, Tomoko Inose, Hitoshi Kasai, Farsai Taemaitree, Hiroshi Uji-i, Kenji Hirai, Beatrice Fortuni
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Journal Title
Advanced Optical Materials
Volume: -
Related Report
Peer Reviewed / Int'l Joint Research
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