Mitochondria-targeted delocalized lipophilic cation complexed with human serum albumin for tumor cell imaging and treatment

Small molecule 5BMF is a novel mitochondria-targeted delocalized lipophilic cation (DLC) with good anti-tumor activity and fluorescence emission suitable for bioimaging. In this study, human serum albumin (HSA) complexed with 5BMF (5BMF@HSA) has been developed to further improve its solubility (from 1.61 to 5.41 mg/mL), and the fluorescent intensity of 5BMF@HSA was improved over 2 times. Nearly 10-fold 5BMF was released from 5BMF@HSA complex in acidic condition when compared with neutral/basic environment. Intracellular distribution of 5BMF was altered by HSA as its signals were observed in lysosomes where free 5BMF barely localized. Both 5BMF@HSA and 5BMF showed selective toxicity toward tumor cells in μM and nM range and effectively inhibited tumor growth in mice model. In summary, 5BMF@HSA shows improved solubility in aqueous buffer and enhanced fluorescence emission, and maintains tumor inhibition capability. It is a promising protein complex for tumor cell imaging and tumor treatment. Description: Binding 5BMF with HSA would enhance its aqueous solubility and fluorescence intensity, while still retaining the small molecule's mitochondria targeting ability. Once accumulated in this organelle of cancer cells, 5BMF@HSA will disrupt mitochondria's abnormally high ΔΨm and lead to its destruction, inducing the death of cancer cells. Also, 5BMF may release from the complex in lysosomes because of the acidic environment. [Display omitted]