Fig 2: Synthesis and characterization of CPC. (A) TEM image of CPC, scale bar: 200 nm. (B) Drug loading curve of CPC. (C) Representative images of CPC-FITC and important intracellular organelles, scale bar: 50 μm. (D) A protein-coated plate experiment demonstrated that CPC could bind to collagen III, TOM20, VDAC2, VDAC1, TOM34, TOM7, TOM70 and TOM40. scale bar: 50 μm. (E) Zeta potential determination of CPC. (F) Quantitative analysis of the protein-coated plate experiment. (G) Cumulative drug release of CPC in the dispersion system at pH = 6.0 and 7.4. (H) O2•- scavenging ability of CPC. (I)•OH scavenging ability of CPC. (J) ONOO− scavenging ability of CPC. (K) H2O2 scavenging ability of CPC.

Fig 3: PDA-mediated mitochondrial targeting. (A) Brief diagram of the Fe3O4@PDA synthesis process, and the selective enrichment and identification of mitochondrial proteins by magnetic separation and protein profile. (B) TEM images of Fe3O4 and Fe3O4@PDA, scale bar: 100 nm and 50 nm. (C) MtROS production of isolated mitochondria detected by flow cytometry using MitoSOX red staining. (D) The GO cellular component classification of mitochondrial proteins bound to Fe3O4@PDA. (E) Identification of MOM-related proteins. MOM-related proteins from GO analysis were further cross-analyzed with the UniProt Rat MOM database. (F) WB of TOM7, TOM20, TOM34, VDAC1/2, TOM40, TOM70 adsorbed on Fe3O4 and Fe3O4@PDA. (G–H) The binding energy of PDA and SUR/TOM40/TOM70/TOM34/TOM20/VDAC2 determined by molecular docking. The blue bonds represent hydrogen bonds; the purple bonds represent hydrophobic interactions; the orange bonds represent π-cations; the red bonds represent π-stacking.