Tumor Microenvironment‐Triggered Aggregation of Antiphagocytosis 99mTc‐Labeled Fe3O4 Nanoprobes for Enhanced Tumor Imaging In Vivo |
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Authors: | Zhenyu Gao Yi Hou Jianfeng Zeng Lei Chen Chunyan Liu Wensheng Yang Mingyuan Gao |
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Affiliation: | 1. College of Chemistry, Jilin University, Changchun, China;2. Institute of Chemistry, Chinese Academy of Sciences, Zhong Guan Cun, Beijing, China;3. Centre for Molecular Imaging and Nuclear Medicine, School for Radiological and Interdisciplinary Sciences (RAD‐X), Soochow University, Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, China;4. School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing, P. R. China |
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Abstract: | A tumor microenvironment responsive nanoprobe is developed for enhanced tumor imaging through in situ crosslinking of the Fe3O4 nanoparticles modified with a responsive peptide sequence in which a tumor‐specific Arg‐Gly‐Asp peptide for tumor targeting and a self‐peptide as a “mark of self” are linked through a disulfide bond. Positioning the self‐peptide at the outmost layer is aimed at delaying the clearance of the nanoparticles from the bloodstream. After the self‐peptide is cleaved by glutathione within tumor microenvironment, the exposed thiol groups react with the remaining maleimide moieties from adjacent particles to crosslink the particles in situ. Both in vitro and in vivo experiments demonstrate that the aggregation substantially improves the magnetic resonance imaging (MRI) contrast enhancement performance of Fe3O4 particles. By labeling the responsive particle probe with 99mTc, single‐photon emission computed tomography is enabled not only for verifying the enhanced imaging capacity of the crosslinked Fe3O4 particles, but also for achieving sensitive dual modality imaging of tumors in vivo. The novelty of the current probe lies in the combination of tumor microenvironment‐triggered aggregation of Fe3O4 nanoparticles for boosting the T2 MRI effect, with antiphagocytosis surface coating, active targeting, and dual‐modality imaging, which is never reported before. |
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Keywords: | antiphagocytosis Fe3O4 nanoparticles sensitive MRI/SPECT imaging tumor microenvironment‐triggered aggregation |
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