Nanoparticle-Based Activatable MRI Probes for Disease Imaging and Monitoring

Abstract

Traditional diagnosis relies on identifying anatomical abnormality, which offers a stage for various anatomical imaging techniques, such as X-ray computed tomography (CT), ultrasonic imaging, and magnetic resonance imaging (MRI). The good capacity of providing anatomical details, especially for soft tissues, popularizes the clinical use of MRI. However, as the understanding of various diseases reaches the molecular level, it is gradually accepted that molecular anomaly often precedes anatomical abnormality. Therefore, molecular imaging, which is aimed at gathering various molecular information in organisms via imaging, starts to gain momentum. Unfortunately, traditional MRI is not capable of molecular imaging. As a result, there is an urgent demand for probes that enable MRI to "see" molecules. A promising design strategy for these probes is to elicit a signal change triggered by the presence of molecular targets, i.e. activation. Benefiting from the rapid development of nanotechnology, a number of nanoparticle-based activatable MRI probes have been developed for molecular imaging. This review summarizes recent advances of activatable MRI nanoprobes for imaging pathological characteristics of cancer, inflammation, and neurodegenerative diseases, with a focus on the design strategies and applications of these probes. In addition, the prospects and challenges of activatable MRI nanoprobes are also discussed.

Recent Advances in Activatable Probes for Molecular Imaging by Stimuli‐Controlled Disassembly

“…As the stimuli-controlled disassembly could induce a distinct size change between nanoparticles and small molecules, the MRI properties (e.g., r 1 relaxivity) could be accordingly changed during the disassembly process in response to a stimulus. [82][83] Particularly, this stimuli-controlled disassembly has shown promise in designing activatable 19 F-MRI probes.…”

Visualization and Quantification of Drug Release by GSH-Responsive Multimodal Integrated Micelles

“…To ensure controlled drug release, stimulus-responsive polymeric micelle drug delivery systems have been investigated. These systems offer enhanced stability in normal tissues and rapid drug release in tumor microenvironments. − Polymeric prodrug micelles containing chemotherapeutic drugs linked with cleavable chemical bonds prevent drug leakage during circulation and respond to stimuli at the tumor site, triggering drug release. − Notably, GSH is crucial in maintaining intracellular redox balance and is associated with various diseases. − Hence, selective detection and quantification of GSH hold valuable information for disease prognosis . Several GSH-responsive drug release systems have been rationally designed for cancer treatment due to the significant difference between intracellular and extracellular GSH concentrations, and tumor cells contain a higher concentration of GSH, which is 4–7 times that of normal cells …”

Furin-Catalyzed Enhanced Magnetic Resonance Imaging Probe for Differential Diagnosis of Malignant Breast Cancers

“…However, tumor-specific molecular information in the lesion tissue could not be detected. Thus, molecular MRI (mMRI) was developed by designing specific probes for molecular visualization in vivo . − In the past few years, researchers have designed a series of mMRI nanoprobes (NPs) with specific responses for disease detection. Han et al reported a peptide-targeted MRI contrast agent (ZD2-Gd 3 N@C80) for sensitive mMRI of extradomain-B fibronectin and showed risk-stratification of BCs .…”