title: In vivo aggregation-induced transition between T1and T2relaxations of magnetic ultra-small iron oxide nanoparticles in tumor microenvironment.
abstract: Surface ligands and their densities may significantly influence the optic, electric, and stable properties of inorganic nanoparticles as well as their magnetic resonance imaging (MRI) characters. In this study, ultra-small iron oxide nanoparticles with hyaluronic acid as surface ligand (Fe3O4@HA) were designed to target tumor cells and tune the T1- and T2-weighted MRI by aggregating in the tumor microenvironment via the degradation of HA upon exposure to hyaluronidase (HAase) with decreasing pH. To realize this purpose, four kinds of Fe3O4@HA nanoparticles with increasing HA density were synthesized and characterized. Fe3O4@HA280, with higher r1value than others, was chosen for the signal modulation test in vitro; the T2signal was enhanced by 36%, and the T1signal decreased by 22% in the presence of HAase and acidic environment during the measurement. However, the chitosan-coated Fe3O4nanoparticles did not show a similar tendency. The overlapping sections in the signal change graph of MDA-MB-231 cells and tumor-bearing mice also validate the self-assembling ability of Fe3O4@HA280. Meanwhile, the tumor mapping graphs indicate the excellent tumor penetration of Fe3O4@HA280, which facilitates this self-assembly process and enhances the interior section contrast of the tumor. This fundamental technique for tuning magnetic properties by the tumor microenvironment may provide a useful strategy for the rational synthesis of other inorganic nanoparticles in the field of tumor diagnostics and therapy.
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanosciences, National Center for Nanoscience and Technology of China, No. 11 Beiyitiao, Zhongguancun, Beijing 100190, P.R. China. chenchy@nanoctr.cn.
authors.forename: Huige
authors.initials: H
authors.lastname: Zhou
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanosciences, National Center for Nanoscience and Technology of China, No. 11 Beiyitiao, Zhongguancun, Beijing 100190, P.R. China. chenchy@nanoctr.cn.
authors.forename: Jinglong
authors.initials: J
authors.lastname: Tang
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanosciences, National Center for Nanoscience and Technology of China, No. 11 Beiyitiao, Zhongguancun, Beijing 100190, P.R. China. chenchy@nanoctr.cn.
authors.forename: Jiayang
authors.initials: J
authors.lastname: Li
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanosciences, National Center for Nanoscience and Technology of China, No. 11 Beiyitiao, Zhongguancun, Beijing 100190, P.R. China. chenchy@nanoctr.cn.
authors.forename: Wanqi
authors.initials: W
authors.lastname: Li
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanosciences, National Center for Nanoscience and Technology of China, No. 11 Beiyitiao, Zhongguancun, Beijing 100190, P.R. China. chenchy@nanoctr.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanosciences, National Center for Nanoscience and Technology of China, No. 11 Beiyitiao, Zhongguancun, Beijing 100190, P.R. China. chenchy@nanoctr.cn.
authors.forename: Chunying
authors.identifier: http://orcid.org/0000-0002-6027-0315
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media; D005290:Ferric Compounds; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D053758:Nanoparticles; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging; D059016:Tumor Microenvironment
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; C000499:ferric oxide