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Colloids Surf B Biointerfaces. 2016 Nov 1;147:387-396. doi: 10.1016/j.colsurfb.2016.08.024. Epub 2016 Aug 18.

A mitochondria targeting Mn nanoassembly of BODIPY for LDH-A, mitochondria modulated therapy and bimodal imaging of cancer.

Author information

1
School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, 212013, PR China; School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China; School of Biological Sciences, Department of Biochemistry, University of Cape Coast, Cape Coast, Ghana.
2
School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, 212013, PR China.
3
Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, PR China.
4
School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China.
5
School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, 212013, PR China. Electronic address: chenqy@ujs.edu.cn.
6
School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China. Electronic address: jinggao@ujs.edu.cn.
7
Beijing National Laboratory for Molecular Science, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, PR China.

Abstract

HIF-1α and LDH-A are important targets for hypoxia-driven drug resistance. Mitochondria targeted fluorescent manganese(II)-complexes can be used as potential fluorescence imaging agents, MRI contrast agents and HIF-1α and LDH-A involved anticancer complexes. In this study, a fluorescent manganese(II) nanoparticle, labeled as (PEG-Mn-BDA), was synthesized and used as both fluorescent and MRI imaging agents in cancer cells. In vitro bioassay results indicate that PEG-Mn-BDA was able to inhibit LDH-A activity and depolarize mitochondrial membrane potential with the generation of intracellular ROS, which contributed to the induction of apoptosis. Moreover, the pro-apoptotic protein, caspase 3 was highly expressed. In vivo, PEG-Mn-BDA could also exert inhibition on a mouse hepatocellular carcinoma xenograft. These results suggest that mitochondria targeted PEG-Mn-BDA was able to simultaneously induce selective inhibition on cancer cells and a mouse carcinoma xenograft, label cancer cells with fluorescence and enhance MRI contrast. Therefore, PEG-Mn-BDA is a good candidate for cancer treatment and imaging.

KEYWORDS:

Anticancer; Apoptosis; Imaging; Manganese nanoparticle; Mitochondria

PMID:
27559997
DOI:
10.1016/j.colsurfb.2016.08.024
[Indexed for MEDLINE]

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