Erlotinib-Conjugated Iron Oxide Nanoparticles as a Smart Cancer-Targeted Theranostic Probe for MRI.
We designed and synthesized novel theranostic nanoparticles that showed the considerable potential for clinical use in targeted therapy, and non-invasive real-time monitoring of tumors by MRI. Our nanoparticles were ultra-small with superparamagnetic iron oxide cores, conjugated to erlotinib (FeDC-E NPs). Such smart targeted nanoparticles have the preference to release the drug intracellularly rather than into the bloodstream, and specifically recognize and kill cancer cells that overexpress EGFR while being non-toxic to EGFR-negative cells. MRI, transmission electron microscopy and Prussian blue staining results indicated that cellular uptake and intracellular accumulation of FeDC-E NPs in the EGFR overexpressing cells was significantly higher than those of the non-erlotinib-conjugated nanoparticles. FeDC-E NPs inhibited the EGFR-ERK-NF-κB signaling pathways, and subsequently suppressed the migration and invasion capabilities of the highly invasive and migrative CL1-5-F4 cancer cells. In vivo tumor xenograft experiments using BALB/c nude mice showed that FeDC-E NPs could effectively inhibit the growth of tumors. T2-weighted MRI images of the mice showed significant decrease in the normalized signal within the tumor post-treatment with FeDC-E NPs compared to the non-targeted control iron oxide nanoparticles. This is the first study to use erlotinib as a small-molecule targeting agent for nanoparticles.
Molecular and Cell Biology, Taiwan International Graduate Program, Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
Ahmed Atef Ahmed
AA
Ali
Department of Medical Imaging, Taipei Medical University Hospital, Taipei 110, Taiwan.|Translational Imaging Research Center, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
Fei-Ting
FT
Hsu
The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
Chia-Ling
CL
Hsieh
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan.
Chia-Yang
CY
Shiau
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
Chiao-Hsi
CH
Chiang
Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan.
Zung-Hang
ZH
Wei
Department of Medical Imaging, Taipei Medical University Hospital, Taipei 110, Taiwan.|Translational Imaging Research Center, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
Cheng-Yu
CY
Chen
Molecular and Cell Biology, Taiwan International Graduate Program, Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.|Graduate Institute for Cancer Biology &Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
Hsu-Shan
HS
Huang
D000818:Animals; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods*; D000069347:Erlotinib Hydrochloride / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000627:therapeutic use* / Q000648:ultrastructure; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism
D003287:Contrast Media; D058185:Magnetite Nanoparticles; D000069347:Erlotinib Hydrochloride