An Activity-Based Sensing Approach to Monitor Nanomaterial-Promoted Changes in Labile Metal Pools in Living Systems
Year: 2026
Type: article
Abstract: Metal-based nanoparticles are a promising class of materials for diagnosis and treatment of cancer and other diseases. However, mechanisms of action of these nanomedicines remain insufficiently understood due in large part to our limited understanding of the dynamic equilibria between solid metal nanoparticles and labile metal ions generated from these nanoparticles within complex biological milieus. Here, we apply activity-based sensing to directly identify and investigate the fate of labile copper pools with metal and oxidation state-specificity generated by anticancer copper nanomedicines. We found that treatment of cells with copper-releasing nanoparticles alter labile Cu-(I)/Cu-(II) ratios through an increase in labile Cu-(II), while overall labile copper levels decrease. Labile copper release triggers compensatory responses in two major antioxidant pathways, glutathione (GSH) and nuclear factor erythroid 2-related factor 2 (NRF2), as well as in metal homeostasis to limit copper availability via regulation of copper export (ATP7B) and copper import (CTR1) proteins. These findings establish the value of activity-based sensing as a generalizable approach for labile metal imaging to help decipher molecular mechanisms of bioactive metal nanoparticles and guide the development of more effective nanomedicine diagnostics and therapies to target metal-dependent disease vulnerabilities.
Source: Chemical & Biomedical Imaging
DOI: 10.1021/cbmi.5c00237
Institutions: Universidad de Zaragoza, Instituto de Salud Carlos III, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine, Instituto de Nanociencia y Materiales de Aragón, Instituto de Investigación Sanitaria Aragón, Princeton University, Lawrence Berkeley National Laboratory
Language: English
Topic: Trace Elements in Health
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: diamond
Funders: U.S. Department of Energy, Princeton University, Canadian Institute for Advanced Research, Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina, Universidad de Zaragoza, National Institutes of Health, Office of Science, Office of the Dean for Research, Princeton University, European Research Council, Instituto de Salud Carlos III, Basic Energy Sciences, Lawrence Berkeley National Laboratory, H2020 European Research Council
Awards: G1079818582, Acquisition of a Cryoprobe and Related Accessories for a 600 MHz NMR Spectrometer to Support Health Research Activities at the University of California, Berkeley, G1143651532, G1286236842, G1286251239, G1414775356, G2857863752, G30714459, G3083819904, G365575497, G382641700, G419881185, G42916606, Catalytic Dual-Function Devices Against Cancer, A Molecular Atlas of the Developing Lung, G4501827968, G4950536974, G498139845, G5849692847, G650090426, G6652958823, G7354628648, CAT - A hybrid IMS-MS platform for ultrasensitive and high resolution glycan analysis, G9000040386, G9000151808, G9000270952, G969889393
OpenAlex ID: W7124252292