Cascaded Multiresponsive Self-Assembled 19F MRI Nanoprobes with Redox-Triggered Activation and NIR-Induced Amplification

Molecular probes featuring promising capabilities including specific targeting, high signal-to-noise ratio, and in situ visualization of deep tissues are in great demand for tumor diagnosis and therapy. 19F magnetic resonance imaging (MRI) techniques incorporating stimuli-responsive probes are anticipated to be highly beneficial for specific detection and imaging of tumors because of negligible background and deep tissue penetration. Herein, we report a cascaded multiresponsive self-assembled nanoprobe, which enables sequential redox-triggered and near-infrared (NIR) irradiation-induced 19F MR signal activation/amplification for sensing and imaging. Specifically, we designed and synthesized a cascaded multiresponsive 19F-bearing nanoprobe based on the self-assembly of amphiphilic redox-responsive 19F-containing polymers and NIR-absorbing indocyanine green (ICG) molecules. It could realize the activation of 19F signals in the reducing tumor microenvironment and subsequent signal amplification via the photothermal process. This stepwise two-stage activation/amplification of 19F signals was validated by 19F NMR and MRI both in vitro and in vivo. The multiresponsive 19F nanoprobes capable of cascaded 19F signal activation/amplification and photothermal effect exertion can provide accurate sensing and imaging of tumors.