Stem cell therapies are increasingly recognized as the future direction of regenerative medicine, but the biological fate of the administrated stem cells remains a major concern for clinical translation, which calls for an approach to efficiently monitoring the stem cell behaviors in vivo. Magnetic particle imaging (MPI) is an emerging technology for cell tracking; however, its utility has been largely restricted due to the lack of optimal magnetic nanoparticle tracers. Herein, by controlled engineering of the size and shape of magnetic nanoparticles tailored to MPI physics theory, a specialized MPI tracer, based on cubic iron oxide nanoparticles with an edge length of 22 nm (CIONs-22), is developed. Due to the inherent lower proportion of disordered surface spins, CIONs-22 exhibit significantly larger saturation magnetization than that of spherical ones, while they possess similar saturation magnetization but smaller coercivity compared to larger-sized CIONs. These magnetic properties of CIONs-22 warrant high sensitivity and resolution of MPI. With their efficient cellular uptake, CIONs-22 exhibit superior MPI performance for stem cell labeling and tracking compared to the commercialized tracer Vivotrax. By virtue of these advantages, CIONs-22 enable real-time and prolonged monitoring of the spatiotemporal trajectory of stem cells transplanted to hindlimb ischemia mice, which demonstrates the great potential of CIONs-22 as MPI tracers to advance stem cell therapies. KEYWORDS: magnetic particle imaging, cubic iron oxide nanoparticle, bone mesenchymal stem cell, stem cell tracking, hindlimb ischemia S tem-cell-based therapies have demonstrated therapeutic potential for a wide spectrum of diseases, such as hindlimb ischemia, stroke, liver disease, and heart failure. 1,2 However, to ultimately advance this fast growing field from preclinical studies to translation, several major concerns are yet to be addressed, one of which is the poorly understood biological fate of injected stem cells, e.g., the timing and path of their migration to diseased tissues. In this regard, it is of particular relevance to monitor stem cells after administration into the body, which would provide valuable information for predicting the therapeutic efficacy, evaluating the potential risk, and optimizing treatment strategies. 3 Current technologies for in vivo stem cell tracking include optical imaging, magnetic resonance imaging (MRI), and radionuclide imaging. 4−7 Optical imaging has single-cell resolution, but its clinical translation is hindered by the poor tissue penetration of the light photon. 8 Radionuclide imaging, with excellent depth penetration, faces the disadvantage of narrow temporal window due to the short half-lives of radionuclide tracers that are also constantly questioned for toxicities. 9,10 MRI offers high spatial resolution and unlimited depth penetration without using radiotracers. 8 However, the dark signal generated by T2-weighed MRI contrast agents (CAs) (e.g., iron oxide nanoparticles (IONPs)) 11,12 can be easil...
Unsatisfactory post-stroke recovery has long been a negative factor in the prognosis of ischemic stroke due to the lack of pharmacological treatments. Mesenchymal stem cells (MSCs)-based therapy has recently emerged as a promising strategy redefining stroke treatment; however, its effectiveness has been largely restricted by insufficient therapeutic gene expression and inadequate cell numbers in the ischemic cerebrum. Herein, a non-viral and magnetic field-independent gene transfection approach is reported, using magnetosome-like ferrimagnetic iron oxide nanochains (MFIONs), to genetically engineer MSCs for highly efficient post-stroke recovery. The 1D MFIONs show efficient cellular uptake by MSCs, which results in highly efficient genetic engineering of MSCs to overexpress brainderived neurotrophic factor for treating ischemic cerebrum. Moreover, the internalized MFIONs promote the homing of MSCs to the ischemic cerebrum by upregulating CXCR4. Consequently, a pronounced recovery from ischemic stroke is achieved using MFION-engineered MSCs in a mouse model.
Nanozymes are nanomaterials with similar catalytic activities to natural enzymes. Compared with natural enzymes, they have numerous advantages, including higher physiochemical stability, versatility, and suitability for mass production. In the past decade, the synthesis of nanozymes and their catalytic mechanisms have advanced beyond the simple replacement of natural enzymes, allowing for fascinating applications in various fields such as biosensing and disease treatment. In particular, the exploration of nanozymes as powerful toolkits in diagnostic viral testing and antiviral therapy has attracted growing attention. It can address the great challenges faced by current natural enzyme‐based viral testing technologies, such as high cost and storage difficulties. Therefore, nanozyme can provide a novel nanozyme‐based antiviral therapeutic regime with broader availability and generalizability that are keys to fighting a pandemic such as COVID‐19. Herein, we provide a timely review of the state‐of‐the‐art nanozymes regarding their catalytic activities, as well as a focused discussion on recent research into the use of nanozymes in viral testing and therapy. The remaining challenges and future perspectives will also be outlined. Ultimately, this review will inform readers of the current knowledge of nanozymes and inspire more innovative studies to push forward the frontier of this field.
The assessment of vascular anatomy and functions using magnetic resonance imaging (MRI) is critical for medical diagnosis, whereas the commonly used low‐field MRI system (≤3 T) suffers from low spatial resolution. Ultrahigh field (UHF) MRI (≥7 T), with significantly improved resolution and signal‐to‐noise ratio, shows great potential to provide high‐resolution vasculature images. However, practical applications of UHF MRI technology for vascular imaging are currently limited by the low sensitivity and accuracy of single‐mode (T1 or T2) contrast agents. Herein, a UHF‐tailored T1–T2 dual‐mode iron oxide nanoparticle‐based contrast agent (UDIOC) with extremely small core size and ultracompact hydrophilic surface modification, exhibiting dually enhanced T1–T2 contrast effect under the 7 T magnetic field, is reported. The UDIOC enables clear visualization of microvasculature as small as ≈140 µm in diameter under UHF MRI, extending the detection limit of the 7 T MR angiography. Moreover, by virtue of high‐resolution UHF MRI and a simple double‐checking process, UDIOC‐based dual‐mode dynamic contrast‐enhanced MRI is successfully applied to detect tumor vascular permeability with extremely high sensitivity and accuracy, providing a novel paradigm for the precise medical diagnosis of vascular‐related diseases.
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