Bio-Inspired Carbon Dots as Malondialdehyde Indicator for Real-Time Visualization of Lipid Peroxidation in Depression

Brain lipidic peroxidation is closely associated with the pathophysiology of various psychiatric diseases including depression. Malondialdehyde (MDA), a reactive aldehyde produced in lipid region, serves as a crucial biomarker for lipid peroxidation. However, techniques enabling real-time detection of MDA are still lacking due to the inherent trade-off between recognition dynamics and robustness. Inspired by the structure of phospholipid bilayers, amphiphilic carbon dots named as CG-CDs targeted to cell membrane are designed for real-time monitoring of MDA fluctuations. The design principle relies on the synergy of dynamic hydrogen bonding recognition and cell membrane targetability. The latter facilitates the insertion of CG-CDs into lipid regions and provides a hydrophobic environment to stabilize the labile hydrogen bonding between CG-CDs and MDA. As a result, recognition robustness and dynamics are simultaneously achieved for CG-CDs/MDA, allowing for in situ visualization of MDA kinetics in cell membrane due to the instant response (<5 s), high sensitivity (9-fold fluorescence enhancement), intrinsic reversibility (fluorescence on/off), and superior selectivity. Subsequently, CG-CDs are explored to visualize nerve cell membrane impairment in depression models of living cells and zebrafish, unveiling the extensive heterogeneity of the lipid peroxidation process and indicating a positive correlation between MDA levels and depression.