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

Abstract

Molecular probes featuring promising capabilities including specific targeting, high signal-to-noise ratio, and <i>in situ</i> 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 <i>in vitro</i> and <i>in vivo</i>. The multiresponsive ¹⁹F nanoprobes capable of cascaded ¹⁹F signal activation/amplification and photothermal effect exertion can provide accurate sensing and imaging of tumors.