Magnetic resonance imaging (MRI) is a noninvasive medical imaging modality that is routinely used in clinics, providing anatomical information with micron resolution, soft tissue contrast, and deep penetration. Exogenous contrast agents increase image contrast by shortening longitudinal (T1) and transversal (T2) relaxation times. Most of the T1 agents used in clinical MRI are based on paramagnetic lanthanide complexes (largely Gd-based). In moving to translatable formats of reduced toxicity, greater chemical stability, longer circulation times, higher contrast, more controlled functionalisation and additional imaging modalities, considerable effort has been applied to the development of nanoparticles bearing paramagnetic ions. This review summarises the most relevant examples in the synthesis and biomedical applications of paramagnetic nanoparticles as contrast agents for MRI and multimodal imaging. It includes the most recent developments in the field of production of agents with high relaxivities, which are key for effective contrast enhancement, exemplified through clinically relevant examples.

The use of nanoparticulate systems as contrast agents for magnetic resonance imaging (MRI) is well-established and known to facilitate an enhanced image sensitivity within scans of a particular pathological region of interest. Such a capability can enable both a non-invasive diagnosis and the monitoring of disease progression/response to treatment. In this review, magnetic nanoparticles that exhibit a bio-responsive MR relaxivity are discussed, with pH-, enzyme-, biomolecular-, and protein-responsive systems considered. The ability of a contrast agent to respond to a biological stimulus provides not only enriched diagnostic capabilities over corresponding non-responsive analogues, but also an improved longitudinal monitoring of specific physiological conditions.

A biomedical contrast agent serves to enhance the visualisation of a specific (potentially targeted) physiological region. In recent years, mesoporous silica nanoparticles (MSNs) have developed as a flexible imaging platform of tuneable size/morphology, abundant surface chemistry, biocompatibility and otherwise useful physiochemical properties. This review discusses MSN structural types and synthetic strategies, as well as methods for surface functionalisation. Recent applications in biomedical imaging are then discussed, with a specific emphasis on magnetic resonance and optical modes together with utility in multimodal imaging.

The polymeric capping of a paramagnetically doped MSN enables the generation of high T1 MRI contrast which is highly pH responsive through a fully reversible change in polymer conformation.

Very high longitudinal relaxivity switches can be obtained with pH-responsive polymer-coated paramagnetic mesoporous silica nanoparticles (MSNs), as the local environment traverses the 〖pK〗_a of the polymer coat (∆r_1 ~ 50...

Paramagnetically-doped polymer micelles, containing an ionizable poly(acrylic acid) (PAA) block, support high-contrast MR imaging at clinically relevant field strengths in a manner that is strongly pH responsive. A reversible switch...

Contrast agents retaining high relaxivities at ultrahigh magnetic fields underpin an enhanced image sensitivity within derived MRI scans. By varying the Dy3+ loading density inside a mesoporous silica architecture the...