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 F-19 magnetic resonance imaging (F-19 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 F-19 atoms in the nanoplatform are significantly different in F-19 nuclear magnetic resonance (NMR) spectra, which facilitates the implementation of ratiometric F-19 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 F-19 MRI signal. Therefore, a linear correlation between the Dox release profile and ratiometric F-19 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 F-19 MRI to visualize drug release in vivo.