An Activity-Based Sensing Approach to Monitor Nanomaterial-Promoted Changes in Labile Metal Pools in Living Systems

Area of Science:

• Nanomedicine
• Biomedical Engineering
• Materials Science

Background:

• Metal-based nanoparticles show promise for cancer diagnosis and treatment.
• Understanding nanomedicine mechanisms requires knowledge of metal ion dynamics in biological environments.

Purpose of the Study:

• To investigate labile copper pools generated by anticancer copper nanomedicines using activity-based sensing.
• To elucidate the molecular mechanisms underlying copper nanomedicine action.

Main Methods:

• Application of activity-based sensing for metal and oxidation state-specific detection of labile copper.
• Treatment of cells with copper-releasing nanoparticles.
• Analysis of copper ion ratios (Cu-(I)/Cu-(II)) and cellular responses.

Main Results:

• Copper nanomedicine treatment altered labile copper ion ratios, increasing labile Cu-(II) while decreasing total labile copper.
• Labile copper release activated antioxidant pathways (glutathione, NRF2) and metal homeostasis mechanisms (ATP7B, CTR1).

Conclusions:

• Activity-based sensing is a valuable tool for imaging labile metals and understanding nanomedicine mechanisms.
• Findings guide the development of effective nanomedicines targeting metal-dependent diseases.