The therapeutic promise of microRNA in cancer has yet to be realized. In this study, we identified and therapeutically exploited a new role for miR-10b at the metastatic site, which links its overexpression to tumor cell viability and proliferation. In the protocol developed, we combined a miR-10b-inhibitory nanodrug with low-dose anthracycline to achieve complete durable regressions of metastatic disease in a murine model of metastatic breast cancer. Mechanistic investigations suggested a potent anti-proliferative, pro-apoptotic effect of the nanodrug in the metastatic cells, potentiated by a cell-cycle arrest produced by administration of the low-dose anthracycline. miR-10b was overexpressed specifically in cells with high metastatic potential, suggesting a role for this miRNA as a metastasis-specific therapeutic target. Taken together, our results implied the existence of pathways that regulate the viability and proliferation of tumor cells only after they have acquired the ability to grow at distant metastatic sites. As illustrated by miR-10b targeting, such metastasis-dependent apoptotic pathways would offer attractive targets for further therapeutic exploration.
Magnetic particle imaging (MPI) is a new imaging modality with the potential for high‐resolution imaging while retaining the noninvasive nature of other current modalities such as magnetic resonance imaging (MRI) and positron emission tomography (PET). It is able to track location and quantities of special superparamagnetic iron oxide nanoparticles without tracing any background signal. MPI utilizes the unique, intrinsic aspects of the nanoparticles: how they react in the presence of the magnetic field, and the subsequent turning off of the field. The current group of nanoparticles that are used in MPI are usually commercially available for MRI. Special MPI tracers are in development by many groups that utilize an iron‐oxide core encompassed by various coatings. These tracers would solve the current obstacles by altering the size and material of the nanoparticles to what is required by MPI. In this review, the theory behind and the development of these tracers are discussed. In addition, applications such as cell tracking, oncology imaging, neuroimaging, and vascular imaging, among others, stemming from the implementation of MPI into the standard are discussed.Level of Evidence: 5Technical Efficacy Stage: 3J. Magn. Reson. Imaging 2020;51:1659–1668.
Noninvasive assessment of pancreatic β-cell mass would tremendously aid in managing type 1 diabetes (T1D). Toward this goal, we synthesized an exendin-4 conjugated magnetic iron oxide–based nanoparticle probe targeting glucagon-like peptide 1 receptor (GLP-1R), which is highly expressed on the surface of pancreatic β-cells. In vitro studies in βTC-6, the β-cell line, showed specific accumulation of the targeted probe (termed MN-Ex10-Cy5.5) compared with nontargeted (termed MN-Cy5.5). In vivo magnetic resonance imaging showed a significant transverse relaxation time (T2) shortening in the pancreata of mice injected with the MN-Ex10-Cy5.5 probe compared with control animals injected with the nontargeted probe at 7.5 and 24 h after injection. Furthermore, ΔT2 of the pancreata of prediabetic NOD mice was significantly higher than that of diabetic NOD mice after the injection of MN-Ex10-Cy5.5, indicating the decrease of probe accumulation in these animals due to β-cell loss. Of note, ΔT2 of prediabetic and diabetic NOD mice injected with MN-Cy5.5 was not significantly changed, reflecting the nonspecific mode of accumulation of nontargeted probe. We believe our results point to the potential for using this agent for monitoring the disease development and response of T1D to therapy.
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