AIEgens Cross-linked Iron Oxide Nanoparticles Synchronously Amplify Bimodal Imaging Signals in Situ by Tumor Acidity-Mediated Click Reaction

摘要

Activatable dual-modal molecular imaging probes present a promising tool for the diagnosis of malignant tumors. However, synchronously enhancing dual-modal imaging signals under a single stimulus is challenging. Herein, we propose an activatable bimodal probe that integrates aggregation-induced emission luminogens (AIEgens) and iron oxide nanoparticles (IOs) to synergistically enhance near-infrared fluorescence (NIRF) intensity and magnetic resonance (MR) contrast through a tumor acidity-mediated click reaction. Tumor acidity-responsive IOs containing dibenzocyclooctyne groups (termed cDIOs) and AIEgens containing azide groups (termed AATs) can be covalently cross-linked in response to tumor acidity, which leads to a simultaneous enhancement in NIRF intensity (approximate to 12.4-fold) and r2 relaxivity (approximate to 2.8-fold). cDIOs and AATs were effectively activated in mice orthotropic breast tumor, and the cross-linking prolonged their retention in tumor, further augmenting the bimodal signals and expanding imaging time frame. This facile strategy leverages the inherent properties of probes themselves and demonstrates promise in future translational studies. @@@ Utilizing the aggregation-enhanced r2 relaxivity of iron oxide nanoparticles and the aggregation-induced emission properties of AIEgens, a non-conjugated/coupled dual-mode probe design strategy is developed to synergistically enhance both near-infrared fluorescence (NIRF) intensity and magnetic resonance contrast.+image

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