Visualization of drug release in a chemo-immunotherapy nanoplatform via ratiometric ¹⁹F magnetic resonance imaging

Visualization of drug release in vivo is crucial for improving therapeutic efficacy and preventing inappropriate medication dosing, yet, challenging. Herein, we report a pH-activated chemo-immunotherapy nanoplatform with visualization of drug release in vivo by ratiometric ¹⁹F magnetic resonance imaging (¹⁹F MRI). This nanoplatform consists of ultra-small histamine-modified perfluoro-15-crown-5-ether (PFCE) nanodroplets loaded with doxorubicin (Dox), which are packaged in trifluoromethyl-containing metal-organic assemblies via coordination-driven self-assembly. The chemical shifts of two types of ¹⁹F atoms in the nanoplatform are significantly different in ¹⁹F nuclear magnetic resonance (NMR) spectra, which facilitates the implementation of ratiometric ¹⁹F MRI without any signal crosstalk. In an acidic tumor microenvironment, this nanoplatform gradually degrades, which results in a sustained drug release with a real-time change in the ratiometric ¹⁹F MRI signal. Therefore, a linear correlation between the Dox release profile and ratiometric ¹⁹F MRI signal is established to visualize Dox release. Moreover, the pH-triggered disassembly of the nanoplatform leads to cell pyroptosis, which evokes immunogenic cell death (ICD), resulting in the regression of the primary tumor and inhibition of distal tumor growth. This study provides the proof-of-concept application of ratiometric ¹⁹F MRI to visualize drug release in vivo.