title: Tumor Microenvironment-Triggered Aggregation of Antiphagocytosis99mTc-Labeled Fe3O4Nanoprobes for Enhanced Tumor Imaging In Vivo.
abstract: A tumor microenvironment responsive nanoprobe is developed for enhanced tumor imaging through in situ crosslinking of the Fe3O4nanoparticles 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 Fe3O4particles. By labeling the responsive particle probe with99mTc, single-photon emission computed tomography is enabled not only for verifying the enhanced imaging capacity of the crosslinked Fe3O4particles, 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 Fe3O4nanoparticles for boosting the T2MRI effect, with antiphagocytosis surface coating, active targeting, and dual-modality imaging, which is never reported before.
authors.affiliation: College of Chemistry, Jilin University, Changchun, 130012, China.|Institute of Chemistry, Chinese Academy of Sciences, Bei Yi Jie 2, Zhong Guan Cun, Beijing, 100190, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Institute of Chemistry, Chinese Academy of Sciences, Bei Yi Jie 2, Zhong Guan Cun, Beijing, 100190, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hou
authors.affiliation: 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, 215123, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zeng
authors.affiliation: 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, 215123, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute of Chemistry, Chinese Academy of Sciences, Bei Yi Jie 2, Zhong Guan Cun, Beijing, 100190, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Liu
authors.affiliation: College of Chemistry, Jilin University, Changchun, 130012, China.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Yang
authors.affiliation: Institute of Chemistry, Chinese Academy of Sciences, Bei Yi Jie 2, Zhong Guan Cun, Beijing, 100190, China.|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, 215123, China.|School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Gao
mesh_terms: D005290:Ferric Compounds; D006801:Humans; D008279:Magnetic Resonance Imaging; D053758:Nanoparticles; D009369:Neoplasms; D013667:Technetium; D015899:Tomography, Emission-Computed, Single-Photon; D059016:Tumor Microenvironment
chemical_list: D005290:Ferric Compounds; C000499:ferric oxide; D013667:Technetium
keywords: Fe3O4 nanoparticles; antiphagocytosis; sensitive MRI/SPECT imaging; tumor microenvironment-triggered aggregation