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

Kun Qian; Hao Chen; Chunrong Qu; Jinxu Qi; Bulin Du; Timothy Ko; Zhanhong Xiang; Martha Kandawa-Schulz; Yihong Wang; Zhen Cheng

doi:10.1016/j.nano.2019.102087

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

Nanomedicine. 2020 Jan:23:102087. doi: 10.1016/j.nano.2019.102087. Epub 2019 Aug 24.

Authors

Kun Qian¹, Hao Chen², Chunrong Qu², Jinxu Qi³, Bulin Du², Timothy Ko², Zhanhong Xiang², Martha Kandawa-Schulz⁴, Yihong Wang⁵, Zhen Cheng⁶

Affiliations

¹ School of Chemistry and Chemical Engineering, Southeast University, Nanjing, China; Molecular Imaging Program at Stanford (MIPS), Bio-X Program, and Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University, California, USA.
² Molecular Imaging Program at Stanford (MIPS), Bio-X Program, and Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University, California, USA.
³ School of Chemistry and Chemical Engineering, Southeast University, Nanjing, China.
⁴ Department of Chemistry and Biochemistry, University of Namibia, Windhoek, Namibia.
⁵ School of Chemistry and Chemical Engineering, Southeast University, Nanjing, China. Electronic address: yihongwang@seu.edu.cn.
⁶ Molecular Imaging Program at Stanford (MIPS), Bio-X Program, and Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University, California, USA. Electronic address: zcheng@stanford.edu.

PMID: 31454551
DOI: 10.1016/j.nano.2019.102087

Abstract

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.

Keywords: Delocalized lipophilic cations; Fluorescence imaging; Human serum albumin; Mitochondria.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Antineoplastic Agents* / chemistry
Antineoplastic Agents* / pharmacology
Breast Neoplasms* / diagnostic imaging
Breast Neoplasms* / drug therapy
Breast Neoplasms* / metabolism
Breast Neoplasms* / pathology
Cell Line, Tumor
Drug Delivery Systems*
Female
Humans
Mice
Mice, Nude
Mitochondria / metabolism*
Mitochondria / pathology
NIH 3T3 Cells
Optical Imaging*
Serum Albumin, Human* / chemistry
Serum Albumin, Human* / pharmacology

Substances

Antineoplastic Agents
Serum Albumin, Human