摘要
Janus nanoparticles （JNPs） have multiple configurations for molecular imaging, targeting, and therapeutic effects on cancers; these properties have made these particles attractive for biomedical applications. Nonetheless, smart strategies for the controlled synthesis in a liquid phase and exploration of the appropriate applications of JNPs remain a challenge. In this study, a unique liquid-phase method was applied to fabricate Mn3O4-TiO2/ZnO/Fe3O4 multifunctional binary transition metal oxide-based JNPs, using the concept of epitaxial growth and lattice mismatch among synthesized materials. Transmission electron microscopy and scanning transmission electron microscopy results revealed that the created materials are embedded in the form of dimers with good dispersion and homogeneous growth in a nonpolar solvent. Pluronic F-127-coated MnBO4- TiO2 JNPs were utilized as a contrast agent in T1-weighted magnetic resonance imaging （MRI） and in photodynamic therapy （PDT） for cancers in vitro and in vivo. In vivo T1-weighted MRI of the heart, liver, and kidneys in mice after intravenous injection of the nanoparticles revealed high sensitivity and biocompatibility of as-synthesized Mn3O4--TiO2 JNPs. Results of synchrotron X-ray fluorescence microscopy mapping showed the stability of the nanocomposites and efficiency of penetration into the cytoplasm and perinuclear area. Inorganic TiO2 photosensitizers showed promising tumor ablation performance in PDT in vitro and in vivo at low intensity of UV irradiation （5.6 mW.cm-2） because of their ultrasmall size and photodegradable stability. These results reveal that multifunctional Mn3O4-TiO2 JNPs enhance a T1-weighted MRI contrast and have excellent properties for PDT and therefore, may be a novel agent for cancer theranostics.
Janus nanoparticles （JNPs） have multiple configurations for molecular imaging, targeting, and therapeutic effects on cancers; these properties have made these particles attractive for biomedical applications. Nonetheless, smart strategies for the controlled synthesis in a liquid phase and exploration of the appropriate applications of JNPs remain a challenge. In this study, a unique liquid-phase method was applied to fabricate Mn3O4-TiO2/ZnO/Fe3O4 multifunctional binary transition metal oxide-based JNPs, using the concept of epitaxial growth and lattice mismatch among synthesized materials. Transmission electron microscopy and scanning transmission electron microscopy results revealed that the created materials are embedded in the form of dimers with good dispersion and homogeneous growth in a nonpolar solvent. Pluronic F-127-coated MnBO4- TiO2 JNPs were utilized as a contrast agent in T1-weighted magnetic resonance imaging （MRI） and in photodynamic therapy （PDT） for cancers in vitro and in vivo. In vivo T1-weighted MRI of the heart, liver, and kidneys in mice after intravenous injection of the nanoparticles revealed high sensitivity and biocompatibility of as-synthesized Mn3O4--TiO2 JNPs. Results of synchrotron X-ray fluorescence microscopy mapping showed the stability of the nanocomposites and efficiency of penetration into the cytoplasm and perinuclear area. Inorganic TiO2 photosensitizers showed promising tumor ablation performance in PDT in vitro and in vivo at low intensity of UV irradiation （5.6 mW.cm-2） because of their ultrasmall size and photodegradable stability. These results reveal that multifunctional Mn3O4-TiO2 JNPs enhance a T1-weighted MRI contrast and have excellent properties for PDT and therefore, may be a novel agent for cancer theranostics.
基金
This project is financially supported by the National Natural Science Foundation of China （Nos. 81550110258 and U1432114）, Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund （the second phase） （to Aiguo Wu, under Grant No. U1501501）, by the China Postdoctoral Research program （No. 2014M561799）, by the Zhejiang Provincial Natural Science Foundation of China （No. BSH1401038）, by the Hundred Talents Program of the Chinese Academy of Sciences （No. 2010-735）, by the Natural Science Foundation of Ningbo （No. 2015A610080）, by the Key Breakthrough Program of the Chinese Academy of Sciences （No. KGZD-EW-T06）, and Bureau of Science and Technology of Ningbo Municipality City （Nos. 2014B82010, 2015Bl1002, and 2015C50004）. The authors appreciate the cooperation of Ningbo University, Shanghai Niumag Company for their time and help. Dr M. Zubair Iqbal is thankful to Chinese Academy of for awarding a PIFI and CAS- TWAS postdoctoral fellowship （No. 2014FFGB0004）. Furthermore, the authors also acknowledged Shanghai Synchrotron Radiation Facility at Line BL15U （No. h15sr0021） used for X-ray fluorescence imaging.
