Abstract
The mitochondrion is a promising target for diagnosis and therapy. Mitochondrial-targeting silica-coated manganese oxide nanoparticles (MnO@SiO2-PPh3 + NPs) were successfully synthesized to explore the mitochondrial cytotoxicity of nanoparticles. The mitochondrial targeting property was confirmed by a laser scanning confocal microscopy experiment. Even after incubation for only 4 h, the cytotoxicity of MnO@SiO2-PPh3 + NPs against cancer cells was obvious; the ATP content was significantly decreased to 40%; and the mitochondrial membrane potential was depleted. All of these results indicated the collapse of mitochondrial function and the start of a cell apoptosis pathway. Our findings suggest that mitochondrial-mediated
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Chen Y, Yin Q, Ji X, Zhang S, Chen H, Zheng Y, Sun Y, Qu H, Wang Z, Li Y, Wang X, Zhang K, Zhang L, Shi J. Manganese oxidebased multifunctionalized mesoporous silica nanoparticles for pHresponsive MRI, ultrasonography and circumvention of MDR in cancer cells. Biomaterials, 2012, 33: 7126–7137
Chen Y, Chen H, Zhang S, Chen F, Sun S, He Q, Ma M, Wang X, Wu H, Zhang L, Shi J. Structure-property relationships in manganese oxide-mesoporous silica nanoparticles used for T1-weighted MRI and simultaneous anti-cancer drug delivery. Biomaterials, 2012, 33: 2388–2398
Shin J, Anisur RM, Ko MK, Im GH, Lee JH, Lee IS. Hollow manganese oxide nanoparticles as multifunctional agents for magnetic resonance imaging and drug delivery. Angew Chem Int Ed, 2009, 48: 321–324
Na HB, Lee JH, An K, Park YI, Park M, Lee IS, Nam DH, Kim ST, Kim SH, Kim SW, Lim KH, Kim KS, Kim SO, Hyeon T. Development of a T1 contrast agent for magnetic resonance imaging using MnO nanoparticles. Angew Chem Int Ed, 2007, 46: 5397–5401
Patricia C, Patricia dela P, Pilar M, Marta M, José María A, Guillermo R, Félix Y, José María GC, Antonio H. Magnetism in nanoparticles: tuning properties with coatings. J Phys-Condens Mat, 2013, 25: 484006
Kim T, Momin E, Choi J, Yuan K, Zaidi H, Kim J, Park M, Lee N, McMahon MT, Quinones-Hinojosa A, Bulte JWM, Hyeon T, Gilad AA. Mesoporous silica-coated hollow manganese oxide nanoparticles as positive T1 contrast agents for labeling and MRI tracking of adipose- derived mesenchymal stem cells. J Am Chem Soc, 2011, 133: 2955–2961
Schick I, Lorenz S, Gehrig D, Schilmann AM, Bauer H, Panthöfer M, Fischer K, Strand D, Laquai F, Tremel W. Multifunctional two-photon active silica-coated Au@MnO Janus particles for selective dual functionalization and imaging. J Am Chem Soc, 2014, 136: 2473–2483
Sahoo B, Devi KSP, Dutta S, Maiti TK, Pramanik P, Dhara D. Biocom patible mesoporous silica-coated superparamagnetic manganese ferrite nanoparticles for targeted drug delivery and MR imaging applications. J Colloid Interf Sci, 2014, 431: 31–41
Zhan QQ, Qian J, Li X, He SL. A study of mesoporous silicaencapsulated gold nanorods as enhanced light scattering probes for cancer cell imaging. Nanotechnology, 2010, 21: 055704
Hu H, Dai A, Sun J, Li X, Gao F, Wu L, Fang Y, Yang H, An L, Wu H, Yang S. Aptamer-conjugated Mn3O4@SiO2 core-shell nanoprobes for targeted magnetic resonance imaging. Nanoscale, 2013, 5: 10447–10454
Yang X, Zhou Z, Wang L, Tang C, Yang H, Yang S. Folate conjugated Mn3O4@SiO2 nanoparticles for targeted magnetic resonance imaging in vivo. Mater Res Bull, 2014, 57: 97–102
Yang H, Zhuang Y, Hu H, Du X, Zhang C, Shi X, Wu H, Yang S. Silica-coated manganese oxide nanoparticles as a platform for targeted magnetic resonance and fluorescence imaging of cancer cells. Adv Funct Mater, 2010, 20: 1733–1741
Yu C, Zhou Z, Wang J, Sun J, Liu W, Sun Y, Kong B, Yang H, Yang S. In depth analysis of apoptosis induced by silica coated manganese oxide nanoparticles in vitro. J Hazard Mater, 2015, 283: 519–528
Smith RA, Hartley RC, Murphy MP. Mitochondria-targeted small molecule therapeutics and probes. Antioxid Redox Sign, 2011, 15: 3021–3038
Ross MF, Kelso GF, Blaikie FH, James AM, Cochemé HM, Filipovska A, Da Ros T, Hurd TR, Smith RAJ, Murphy MP. Lipophilic triphenylphosphonium cations as tools in mitochondrial bioenergetics and free radical biology. Biochemistry, 2005, 70: 222–230
Liberman EA, Topaly VP, Tsofina LM, Jasaitis AA, Skulachev VP. Mechanism of coupling of oxidative phosphorylation and the membrane potential of mitochondria. Nature, 1969, 222: 1076–1078
Murphy MP, Smith RAJ. Targeting antioxidants to mitochondria by conjugation to lipophilic cations. Annu Rev Pharmacol, 2007, 47: 629–656
Rokitskaya TI, Sumbatyan NV, Tashlitsky VN, Korshunova GA, An tonenko YN, Skulachev VP. Mitochondria-targeted penetrating cations as carriers of hydrophobic anions through lipid membranes. Biochim Biophys Acta, 2010, 1798: 1698–1706
Pang CC, Sun WJ, Xiao D, Ding L, Bu HF. Novel 2H-pyrazolo[4,3- c]hexahydropyridine derivatives: synthesis, crystal structure, fluorescence properties and cytotoxicity evaluation against human breast cancer cells. Sci China Chem, 2013, 56: 702–715
Zhang CN, Wang W, Wang CH, Tian Q, Hang W, Yuan Z, Chen XS. Cytotoxicity of liver targeted drug-loaded alginate nanoparticles. Sci China Chem, 2009, 52: 1382–1387
Du W, Xu X, Zhang D, Lu Q, Gao F. Green synthesis of MnOx nanostructures and studies of their supercapacitor performance. Sci China Chem, 2015, 58: 1–7
Park SY, Oh KT, Oh YT, Oh NM, Youn YS, Lee ES. An artificial photosensitizer drug network for mitochondria-selective photodynamic therapy. Chem Commun, 2012, 48: 2522–2524
Reers M, Smiley ST, Mottola-Hartshorn C, Chen A, Lin M, Chen LB. Mitochondrial membrane potential monitored by JC-1dye. Methods Enzymol, 1995, 260: 406–417
Perelman A, Wachtel C, Cohen M, Haupt S, Shapiro H, Tzur A. JC-1: alternative excitation wavelengths facilitate mitochondrial membrane potential cytometry. Cell Death Dis, 2012, 3: e430
Lemasters JJ, Nieminen AL, Qian T, Trost LC, Elmore SP, Nishimura Y, Crowe RA, Cascio WE, Bradham CA, Brenner DA, Herman B. The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy. Biochim Biophys Acta, 1998, 1366: 177–196
Murphy MP, Smith RAJ. Drug delivery to mitochondria: the key to mitochondrial medicine. Adv Drug Deliver Rev, 2000, 41: 235–250
Yaffe MP. The Machinery of mitochondrial inheritance and behavior. Science, 1999, 283: 1493–1497
Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, Beebe D, Oates PJ, Hammes HP, Giardino I, Brownlee M. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature, 2000, 404: 787–790
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wei, J., Yu, C., Wang, L. et al. Cytotoxicity of mitochondrial-targeting silica-coated manganese oxide nanoparticles. Sci. China Chem. 58, 1537–1543 (2015). https://doi.org/10.1007/s11426-015-5374-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11426-015-5374-1