Core-interlayer-shell Fe3O4@mSiO2@lipid-PEG-methotrexate nanoparticle for multimodal imaging and multistage targeted chemo-photodynamic therapy.
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@mSiO2@lipid-PEG-methotrexatenanoparticle(FMLM), in which the Fe3O4core could be used for magnet-stimulate-response drug release, magnetic resonance imaging, and early-phase magnet targeting ability; the mSiO2layer 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/ZnPc-Fe3O4@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.
Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Science, Xiamen University, Xiamen 361002, China.
Guihua
G
Liu
Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Science, Xiamen University, Xiamen 361002, China.
Jinyuan
J
Ma
Department of Biomaterials, College of Materials, Xiamen University, Xiamen 361005, China.
Yang
Y
Li
Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Science, Xiamen University, Xiamen 361002, China.
Qi
Q
Li
Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen 361005, China.
Chunhua
C
Tan
Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Science, Xiamen University, Xiamen 361002, China.
Hua
H
Song
Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen 361005, China.
Shuhui
S
Cai
Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Science, Xiamen University, Xiamen 361002, China.
Dengyue
D
Chen
Department of Biomaterials, College of Materials, Xiamen University, Xiamen 361005, China.
Zhenqing
Z
Hou
Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Science, Xiamen University, Xiamen 361002, China. Electronic address: chenqing@xmu.edu.cn.
Qing
Q
Chen
Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Science, Xiamen University, Xiamen 361002, China. Electronic address: zhuxuan@xmu.edu.cn.
Xuan
X
Zhu
D000072283:A549 Cells; D000818:Animals; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D058185:Magnetite Nanoparticles / Q000008:administration & dosage*; D008727:Methotrexate / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D064847:Multimodal Imaging / Q000379:methods*; D010778:Photochemotherapy / Q000379:methods*; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D012822:Silicon Dioxide / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D058185:Magnetite Nanoparticles; D011092:Polyethylene Glycols; D012822:Silicon Dioxide; D008727:Methotrexate
Chemo-photodynamic therapy; Dox/ZnPc; Fe(3)O(4)@mSiO(2)@lipid-PEG-methotrexate; Multimodal imaging; Multistage targeted