Mitochondria-Localized Self-Reporting Small-Molecule-Decorated Theranostic Agents for Cancer-Organelle Transporting and Imaging

Recently, fluorescent dyes with a structure-inherent mitochondria-targeting capability have obtained great attention as single-molecule self-reporting theranostic agents to distinguish cancer cells from normal cells. However, there was little attempt using these dyes as a self-reporting ligand for cancer-targeted delivery of nanomaterials or drugs for personalized therapy. Herein, we developed a mitochondria-localized multifunctional nanodelivery system for cancer-targeted drug delivery and dual-modal imaging. First, a series of cyanine-structural small molecules with different-charged substituent groups have been screened based on their mitochondria targeting capability. Furthermore, the cyanine-structural molecule with the best mitochondria-targeting ability was decorated on iron oxide nanoparticles (IONP) for dual-modal imaging. The nanoprobes entered into the cancer cell via the organic anion transporting polypeptide (OATP) pathway and anchored on mitochondria due to the strong interaction between the negative mitochondria membrane and the lipophilic cationic cyanine dye. This work opened an avenue using small molecules with structure-inherent-targeting and self-reporting characteristics as a chemical ligand to develop cancer-targeting and subcellular-localized delivery system.