Mitochondria-Targeted Au@Carbon Dot Nanoprobes for SERS Analysis of Drug-Induced Mitophagy

Mitophagy is closely associated with various diseases. Precise monitoring of its dynamics and understanding its mechanisms are crucial for diagnosing and treating mitophagy-related diseases. This study developed a mitochondria-targeted (MT) surface-enhanced Raman scattering (SERS) nanoprobe to investigate the drug-induced mitophagy through unveiling the mitochondria-related metabolic profiling. The MT-SERS nanoprobe is consist of carbon dots coated with gold nanoparticles functionalized with triphenylphosphonium (Au@CDs-TPP) that exhibits exceptional SERS performance, low cytotoxicity, and mitochondria targeting specificity. Au@CDs-TPP is first used to monitor the classic mitophagy triggered by carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), which demonstrates the diverse metabolic profiling related to mitochondria, like degradation in mitochondrial protein, DNA damage, decreased lipid and cytochrome c content, and increased carbohydrate consumption. We further evaluate the cellular response to anesthetic lidocaine, which can also induce mitophagy in HepG2 cells like FCCP. However, the molecular alterations in lidocaine-induced mitophagy fluctuated differentially compared to that in FCCP-induced mitophagy.