title: A mitochondria targeting Mn nanoassembly of BODIPY for LDH-A, mitochondria modulated therapy and bimodal imaging of cancer.
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.
authors: 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.
authors: Daniel
authors: D
authors: Boison
authors: School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, 212013, PR China.
authors: Wen-Long
authors: WL
authors: Lu
authors: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, PR China.
authors: Qin-Mei
authors: QM
authors: Xu
authors: School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, 212013, PR China.
authors: Huang
authors: H
authors: Yang
authors: School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China.
authors: Tao
authors: T
authors: Huang
authors: School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, 212013, PR China. Electronic address: chenqy@ujs.edu.cn.
authors: Qiu-Yun
authors: QY
authors: Chen
authors: School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China. Electronic address: jinggao@ujs.edu.cn.
authors: Jing
authors: J
authors: Gao
authors: 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.
authors: Yao
authors: Y
authors: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001896:Boron Compounds / Q000737:chemistry*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry; D007770:L-Lactate Dehydrogenase / Q000737:chemistry*; D000080864:Lactate Dehydrogenase 5; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology*; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D005456:Fluorescent Dyes; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D053148:Caspase 3
keywords: Anticancer; Apoptosis; Imaging; Manganese nanoparticle; Mitochondria