Development of MR Nanoprobing Technique for Non-Small Cell Lung Cancer to Achieve Simultaneous Imaging and Drug Delivery
Date Issued
2011
Date
2011
Author(s)
Pan, Chia-Hsin
Abstract
Molecular imaging is the technology that combined molecular biology and clinical medicine in the biomedical field. The goal of this study is to develop a bi-functional contrast agent used in magnetic resonance image (MRI) to achieve the simultaneous imaging and therapy on xenograft non-small cell lung cancer (NSCLC) murine model.
The gefitinib is the targeting drug which is specifically efficient to NSCLC patient with EGFR mutation, it functionalized to inhibit the tyrosine kinase of EGFR for blocking the signal transduction pathway. The small molecules of modified gefitinib were conjugated on the surface of aqueous Fe3O4 nanoparticles, and it delivered through the blood system to the tumor site since the abundant blood vessels and leaky epithelium of tumors.
To incorporate the gefitinib and Fe3O4 nanoparticles, we substituted the weak portion of inhibitors with carbon chain, here we called it as “modified gefitinib”. Further, the modified gefitinib and Fe3O4 nanoparticles were incorporated by N-(3-Dimethylamino propyl) -N’-ethylcarbodiimide hydrochloride (EDC).
The in vitro assays showed both of the modified gefitinib and Fe3O4@gefitinib efficiently inhibited the cell viability, and cell apoptosis were dramatically induced by Fe3O4@gefitinib in EGFR mutant PC9 cells, whereas the wild-type EGFR A549 cells were not. In vitro assays demonstrated the Fe3O4@gefitinib with specificity of cell inhibitory to PC9 cells. In vivo assay showed the tumor was negative enhanced and signal intensity dropped 15% in T2-weighted imaging after Fe3O4@gefitinib administration 4~8 hours, while the muscle tissue presented less than 5% change. Furthermore, we provided the Prussian’s iron staining of tumor histology to verify the Fe3O4@gefitinib accumulated at tumor site substantially than other organs. As the result, it demonstrated that the Fe3O4@gefitinib could target to tumor through the blood circulation system. We also performed some preliminary study to verify the feasibility of MR technique applied in treatment response evaluation for PC9 animal model.
Herein, we produced the bi-functional nanocontrast agent Fe3O4@gefitinib to achieve imaging and therapy simultaneous. In the future, except the improvement of chemical synthesis as well as we would work towards the treatment efficiency evaluation, quantification and prognosis for NSCLC.
Subjects
Non-small cell lung cancer
iron oxide
SDGs
Type
thesis
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