Extracellular vesicle drug occupancy enables real-time monitoring of targeted cancer therapy.

Autor: Pan S; Institute for Health Innovation & Technology, National University of Singapore, Singapore, Singapore., Zhang Y; Institute for Health Innovation & Technology, National University of Singapore, Singapore, Singapore.; Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore., Natalia A; Institute for Health Innovation & Technology, National University of Singapore, Singapore, Singapore.; Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore., Lim CZJ; Institute for Health Innovation & Technology, National University of Singapore, Singapore, Singapore.; Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore., Ho NRY; Institute for Health Innovation & Technology, National University of Singapore, Singapore, Singapore.; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore., Chowbay B; Clinical Pharmacology Laboratory, National Cancer Centre Singapore, Singapore, Singapore.; Centre for Clinician-Scientist Development, Duke-NUS Medical School, Singapore, Singapore.; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore., Loh TP; Institute for Health Innovation & Technology, National University of Singapore, Singapore, Singapore.; Department of Laboratory Medicine, National University Hospital, Singapore, Singapore., Tam JKC; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Shao H; Institute for Health Innovation & Technology, National University of Singapore, Singapore, Singapore. huilin.shao@nus.edu.sg.; Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore. huilin.shao@nus.edu.sg.; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore. huilin.shao@nus.edu.sg.; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. huilin.shao@nus.edu.sg.
Jazyk: angličtina
Zdroj: Nature nanotechnology [Nat Nanotechnol] 2021 Jun; Vol. 16 (6), pp. 734-742. Date of Electronic Publication: 2021 Mar 08.
DOI: 10.1038/s41565-021-00872-w
Abstrakt: Current technologies to measure drug-target interactions require complex processing and invasive tissue biopsies, limiting their clinical utility for cancer treatment monitoring. Here we develop an analytical platform that leverages circulating extracellular vesicles (EVs) for activity-based assessment of tumour-specific drug-target interactions in patient blood samples. The technology, termed extracellular vesicle monitoring of small-molecule chemical occupancy and protein expression (ExoSCOPE), utilizes bio-orthogonal probe amplification and spatial patterning of molecular reactions within matched plasmonic nanoring resonators to achieve in situ analysis of EV drug dynamics. It measures changes in drug occupancy and protein composition in molecular subpopulations of EVs. When used to monitor various targeted therapies, the ExoSCOPE revealed EV signatures that closely reflected cellular treatment efficacy. We further applied the technology for clinical cancer diagnostics and treatment monitoring. Using a small volume of blood, the ExoSCOPE accurately classified disease status and rapidly distinguished between targeted treatment outcomes, within 24 h after treatment initiation.
Databáze: MEDLINE
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