Fluorinated ion liquids (ILs) act as a new type of fluorine agents to build a fluorinated ionic liquid-based activatable 19 F MRI platform (FILAMP). Upon biological stimulation, the coating polymer dissolves or degrades to release the payload, which rapidly enhances the 19 F signals. This ''turn-on'' response is verified by successful detection of biological targets in vitro and in vivo. In summary, FILAMP can serve as a type of activatable 19 F probes for diagnosis and monitoring of biological and pathological processes.

Engineered magnetic nanoparticles have been extensively explored for magnetic resonance imaging (MRI) diagnosis of a tumor to improve the visibility. However, most of these nanoparticles display “always-on” signals without tumor specificity, causing insufficient contrast and false positives. Here, we provide a new paradigm of MRI diagnosis using MnCO3 nanorhombohedras (MnNRs) as an ultrasensitive T 1-weighted MRI contrast agent, which smartly enhances the MR signal in response to the tumor microenvironment. MnNRs would quickly decompose and release Mn2+ at mild acidity, one of the pathophysiological parameters associated with cancer malignancy, and then Mn2+ binds to surrounding proteins to achieve a remarkable amplification of T 1 relaxivity. In vivo MRI experiments demonstrate that MnNRs can selectively brighten subcutaneous tumors from the edge to the interior may be because of the upregulated vascular permeation at the tumor edge, where cancer cell proliferation and angiogenesis are more active. Specially, benefiting from the T 2 shortening effect in normal liver tissues, MnNRs can detect millimeter-sized liver metastases with an ultrahigh contrast of 294%. The results also indicate an effective hepatic excretion of MnNRs through the gallbladder. As such, this pH-activatable MRI strategy with facility, biocompatibility, and excellent efficiency may open new avenues for tumor malignancy and metastasis diagnosis and holds great promise for precision medicine.

Multicolor imaging, which maps the distribution of different targets, is important for in vivo molecular imaging and clinical diagnosis. Fluorine 19 magnetic resonance imaging ( 19 F MRI) is a promising technique because of unique insights without endogenous background or tissue penetration limit. Thus multicolor 19 F MRI probes, which can sense a wide variety of molecular species, are expected to help elucidate the biomolecular networks in complex biological systems. Here, a versatile model of activatable probes based on fluorinated ionic liquids (ILs) for multicolor 19 F MRI is reported. Three types of ILs at different chemical shifts are loaded in nanocarriers and sealed by three stimuli-sensitive copolymers, leading to "off" 19 F signals. The coating polymers specifically respond to their environmental stimuli, then degrade to release the loaded ILs, causing 19 F signals recovery. The nanoprobes are utilized for non-invasive detection of tumor hallmarks, which are distinguished by their individual colors in one living mouse, without interference between each other. This multicolor imaging strategy, which adopts modular construction of various ILs and stimuli-responsive polymers, will allow more comprehensive sensing of multiple biological targets, thus, opening a new realm in mechanistic understanding of complex pathophysiologic processes in vivo.

Ferroptosis has been realized in anticancer drug–induced acute cardiac/kidney injuries (ACI/AKI); however, molecular imaging approach to detect ferroptosis in ACI/AKI is a challenge. We report an artemisinin-based probe (Art-Gd) for contrast-enhanced magnetic resonance imaging of ferroptosis (feMRI) by exploiting the redox-active Fe(II) as a vivid chemical target. In vivo, the Art-Gd probe showed great feasibility in early diagnosis of anticancer drug–induced ACI/AKI, which was at least 24 and 48 hours earlier than the standard clinical assays for assessing ACI and AKI, respectively. Furthermore, the feMRI was able to provide imaging evidence for the different mechanisms of action of ferroptosis-targeted agents, either by blocking lipid peroxidation or depleting iron ions. This study presents a feMRI strategy with simple chemistry and robust efficacy for early evaluation of anticancer drug–induced ACI/AKI, which may shed light on the theranostics of a variety of ferroptosis-related diseases.

Engineered magnetic nanoparticles combining diagnosis and therapy functions into one entity hold great potential to rejuvenate cancer treatment, however, they are still constrained by the “always on” signals and unsatisfactory...