Abstract

AbstractPhotoacoustic (PA) imaging has received great attention in the field of biomedical applications due to the combination advantages of the high contrast of optical imaging and the high spatial resolution of ultrasound. The limited targeting property of PA contrast agents is restricted to elaborate its advantage. To overcome this point, a pretargeting strategy is developed to amplify the targeting property and PA imaging of a model dye in vivo. As a proof of concept, the dibenzyl cyclootyne (DBCO)‐modified Fe@Fe3O4 nanoparticles (NPs) (Fe@Fe3O4/DBCO) and azide‐modified Cy7.5 (Cy7.5‐N3) are adopted as the pretargeting and PA contrast agents, respectively. Fe@Fe3O4/DBCO NPs are first targeted into tumors by the enhanced permeability and retention effect, and then Cy7.5‐N3 is conjugated to the pretargeted Fe@Fe3O4/DBCO labeled tumor cells via strain‐promoted alkyne azide cycloaddition reaction after intravenous injection, which results in an obvious increase of the accumulated dose and PA signal of Cy7.5 in tumor, and simultaneously extends its residence time. This signal amplification strategy should have an important guiding significance for the clinical application in cancer theranostics.

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