細胞種特異的輸送系統の輸送効率を評価する革新的な方法

 In drug administration, drug delivery efficiency for the target cells, tissue and organ needs to be confirmed ideally in order to minimize side effect. However, this analysis in human (clinically) is difficult and formidable task. For example, in the optical analysis, we need to make choice for suitable wavelength (generally long wavelength) due to limited transmittivity of tissues and make the specific labeling maker adhere to the drug. Therefore, we need to consider about more rational analysis method clinically. Liquid biopsy is promising, because we can investigate about the bio-information through the actual patient blood in ex-vivo and in a simple way.
 Sijun Pan, Yan Zhang et al. find an innovative way to evaluate drug delivery efficiency(1). They focus on the extracellular vesicle like exosome as a carrier having drug-delivered traces. For example, in cancer chemotherapy, the extracellular vesicles with the drug protein are secreted in blood. They find the way to differentiate the extracellular vesicle with and without drug protein through labelling using optical-responsive protein and enzyme(1)(See Fig.1a). These protein and enzyme are reactive to specific optical signal, so we can evaluate the degree of the extracellular vesicle with/without drug component in blood sample through optical irradiation in ex-vivo. In the extracellular vesicle with drug, these labelling maker cannot bind the receptors in the vesicle(1)(See Fig.1b).
 This method can be applied to the evaluation of the cell-specific delivery system. Please see my attached note. In the cell-specific delivery system, we decide the target surface protein as an anchor in the target cells (ex. Cancer cell). Probably, some of extracellular vesicles secreted from the target cells have this target surface protein. Therefore, if the nanoparticles we design are delivered to the target site, some traces by drug administration can be found in the specific extracellular vesicles from the target cells. For example, the residues from the nanoparticle drug bind to the surface protein on the extracellular vesicle from the target cells. Therefore, as Ref.(1), the discrimination between bare and drug-perturbative extracellular vesicles via labelling could be realized after blood collection. The target for discrimination is not only surface protein residue, but also infused drugs. In this concept, we may be able to evaluate the drug delivery efficiency in the cell-specific delivery system. This is one of prerequisites to achieve aim of the cell-specific delivery system that we minimize the side effect and maximize the drug effect. In this method, we need to find the effective surface protein and the effective extracellular vesicle specific to the lesion. Some conditions for realization exist including the extracellular vesicle with surface protein specific to the target cells.

 
(Reference)
(1)
Sijun Pan, Yan Zhang, Auginia Natalia, Carine Z. J. Lim, Nicholas R. Y. Ho, Balram Chowbay, Tze Ping Loh, John K. C. Tam & Huilin Shao
Extracellular vesicle drug occupancy enables real-time monitoring of targeted cancer therapy
Nature Nanotechnology volume 16, pages734–742 (2021)
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Author information
Author notes
These authors contributed equally: Sijun Pan, Yan Zhang.
Affiliations
Institute for Health Innovation & Technology, National University of Singapore, Singapore, Singapore
Sijun Pan, Yan Zhang, Auginia Natalia, Carine Z. J. Lim, Nicholas R. Y. Ho, Tze Ping Loh & Huilin Shao
Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore
Yan Zhang, Auginia Natalia, Carine Z. J. Lim & Huilin Shao
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore
Nicholas R. Y. Ho & Huilin Shao
Clinical Pharmacology Laboratory, National Cancer Centre Singapore, Singapore, Singapore
Balram Chowbay
Centre for Clinician-Scientist Development, Duke-NUS Medical School, Singapore, Singapore
Balram Chowbay
Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore
Balram Chowbay
Department of Laboratory Medicine, National University Hospital, Singapore, Singapore
Tze Ping Loh
Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
John K. C. Tam & Huilin Shao