Tumor Microenvironment‐Triggered Aggregation of Antiphagocytosis 99mTc‐Labeled Fe3O4 Nanoprobes for Enhanced Tumor Imaging In Vivo

Abstract

A tumor microenvironment responsive nanoprobe is developed for enhanced tumor imaging through in situ crosslinking of the Fe 3 O 4 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 Fe 3 O 4 particles. By labeling the responsive particle probe with 99m Tc, single‐photon emission computed tomography is enabled not only for verifying the enhanced imaging capacity of the crosslinked Fe 3 O 4 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 Fe 3 O 4 nanoparticles for boosting the T2 MRI effect, with antiphagocytosis surface coating, active targeting, and dual‐modality imaging, which is never reported before.