Magnetic resonance imaging (MRI) has been widely used for disease diagnosis because it can noninvasively obtain anatomical details of various diseases through accurate contrast between soft tissues. Over one‐third of MRI examinations are performed with the assistance of contrast agents. Traditional contrast agents typically display an unchanging signal, thus exhibiting relatively low sensitivity and poor specificity. Currently, advances in stimulus‐responsive contrast agents which can alter the relaxation signal in response to a specific change in their surrounding environment provide new opportunities to overcome such limitation. The signal changes based on stimulus also reflects the physiological and pathological conditions of the site of interests. In this review, how to design stimulus‐responsive nanoparticle MRI contrast agents from the perspective of theory and surface design is comprehensively discussed. Key structural features including size, clusters, shell features, and surface properties are used for tuning the T1 and T2 relaxation properties. The reversible or non‐reversible signal changes highlight the contrast agents have undergone structural changes based on certain stimulus, as an indication for disease diagnosis or therapeutic efficacy.
Osteoporosis is a skeletal disorder resulted in significant structural and functional changes, arousing a wide concern for the high prevalence and cost. Imbalance between osteoclastogenesis and osteogenesis have been verified as a main pathology etiology and considered an efficient therapy target in both clinical and pre-clinical studies. In recent years, inorganic nanomaterials have shown provable activities on osteoclastogenesis inhibition and osteogenesis promotion, respectively. Hence, in this study, a class of hydroxyapatite coated superparamagnetic iron oxide nanoparticles (SPIO@HA) were developed with a core−shell structure for targeting both osteoclastogenesis and osteogenesis. The optimal ratio of SPIO@15HA (Fe/Ca = 1:15, mol/mol) was screened to obtain dual function for inducing both bone formation and preventing bone resorption. The obtained nanocomposites significantly prevented the bone loss of ovariectomized (OVX) mice and increased bone mineral density (BMD) by 9.4%, exhibiting high bone accumulation in magnetic resonance imaging evaluation and reasonable biosafety profile. The mechanism study revealed that SPIO@15HA can suppress bone marrow monocyte derived osteoclast differentiation through TRAF6−p62−CYLD signaling complex regulation. Meanwhile, it could activate MSC osteogenic differentiation by TGF-β, PI3K-AKT and calcium signaling pathway regulation. Moreover, incubation of SPIO@15HA with MSC resulted in several cytokines overexpression such as osteoprotegerin (OPG), CSF2, CCL2 etc., which are responsible for maintaining the bone remodeling balance. The dual function of as-prepared SPIO@15HA may find a new way for designing of inorganic components containing core/shell nanomaterials for osteoporosis treatment.
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