期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 521, 期 1-2, 页码 19-32出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2017.01.068
关键词
Fe3O4@mSiO(2)@lipid-PEG-methotrexate; Multistage targeted; Multimodal imaging; Chemo-photodynamic therapy; Dox/ZnPc
资金
- National Natural Science Foundation of China [31300285, 31100717]
- Social Development Guidance (Key) Project of Fujian Province [2014Y0074]
- Natural Science Foundation of Fujian Province [2015J01348]
- Project of Xiamen science and Technology Bureau [3502Z20163004]
- Specialized Research Fund for the Doctoral Program of Higher Education [20110073120072]
- Multidisciplinary Project Cultivation Research Fund of Shanghai Jiao Tong University [YG2012MS10, YG2012MS31]
Multimodal imaging-guided multistage targeted synergistic combination therapy possesses many advantages including increased tumoricidal effect, reduced toxicity, and retarded drug resistance. Herein, we have elaborately developed a core-interlayer-shell structure Fe3O4@mSiO(2)@lipid-PEG-methotrexatenanoparticle( FMLM), in which the Fe3O4 core could be used for magnet-stimulate-response drug release, magnetic resonance imaging, and early-phase magnet targeting ability; the mSiO(2) layer could encapsulate anticancer drug doxorubicin (Dox) for chemotherapy; and the protective shell of lipid-PEG and lipid-PEG-methotrexate offered later-phase specific cellular targeting ability, good water dispersibility, and loading of photosensitizer zinc phthalocyanine (ZnPc) for simultaneous near-infrared fluorescence imaging and photodynamic therapy. Both in vitro and in vivo studies indicated that the both Dox and ZnPc-loaded FMLM (Dox/ZnPc-FMLM) exhibited the enhanced tumor accumulation, increased cellular uptake, improved anticancer activity, and weaked side effects compared with Dox/ZnPcFe3O4@ mSiO2@lipid-PEG nanoparticle (Dox/ZnPc-FML) and free drug. For the first time, magnet targeting cooperative with methotrexate macromolecular prodrug targeting is successfully exploited to develop a promising versatile theranostic nanoplatform for dual-modal fluorescence and magnetic resonance imaging-guided combined chemo-photodynamic cancer therapy. (C) 2017 Elsevier B. V. All rights reserved.
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