Intranasal delivery of mesenchymal stem cells (MSCs) to the olfactory bulb is a promising approach for treating olfactory injury. Additionally, using the homing phenomenon of MSCs may be clinically applicable for developing therapeutic cell carriers. Herein, using superparamagnetic iron oxide nanoparticles (SPIONs) and a permanent magnet, we demonstrated an enhanced homing effect in an olfactory model. Superparamagnetic iron oxide nanoparticles with rhodamine B (IRBs) had a diameter of 5.22 ± 0.9 nm and ζ-potential of +15.2 ± 0.3 mV. IRB concentration of 15 µg/mL was injected with SPIONs into MSCs, as cell viability significantly decreased when 20 μg/mL was used (p ≤ 0.005) compared to in controls. The cells exhibited magnetic attraction in vitro. SPIONs also stimulated CXCR4 (C-X-C chemokine receptor type 4) expression and CXCR4-SDF-1 (Stromal cell-derived factor 1) signaling in MSCs. After injecting magnetized MSCs, these cells were detected in the damaged olfactory bulb one week after injury on one side, and there was a significant increase compared to when non-magnetized MSCs were injected. Our results suggest that SPIONs-labeled MSCs migrated to injured olfactory tissue through guidance with a permanent magnet, resulting in better homing effects of MSCs in vivo, and that iron oxide nanoparticles can be used for internalization, various biological applications, and regenerative studies.

Stem cells possess a promising potential in the clinical field. The application and effective delivery of stem cells to the desired target organ or site of injury plays an important role. This review describes strategies on understanding the effective delivery of stem cells labeled with superparamagnetic iron oxide nanoparticles (SPION) using an external magnet to enhance stem cell migration in vivo and in vitro. Fourteen total publications among 174 articles were selected. Stem cell type, SPION characteristics, labeling time, and magnetic force in vivo are considered important factors affecting the effective delivery of stem cells to the homing site. Most papers reported that the efficiency was increased when magnet is applied compared to those without. Ten studies analyzed the homing competency of SPION-labeled MSCs in vitro by observing the migration of the cell toward the external magnet. In cell-based experiments, the mechanism of magnetic attraction, the kind of nanoparticles, and various stem cells were studied well. Meta-analysis has shown the mean size of nanoparticles and degree of recovery or regeneration of damaged target organs upon in vivo studies. This strategy may provide a guideline for designing studies involving stem cell homing and further expand stem cell.

Photothermal therapy (PTT) at mild temperatures ranging from 44 to 45 °C holds tremendous promise as a strategy for inducing potent immunogenic cell death (ICD) within tumor tissues, which can reverse the immunosuppressive tumor microenvironment (ITM) into an immune-responsive milieu. However, accurately and precisely controlling the tumor temperature remains a formidable challenge. Here, we report the precision photothermal immunotherapy by using silica-coated gold nanorods (AuNR@SiO ₂ ), and investigating the optimal administration routes and treatment protocols, which enabled to achieve the sustained and controlled mild heating within the tumor tissues. First, the highest photothermal performance of AuNR@SiO ₂ with 20-nm silica shell thickness than 5 or 40 nm was confirmed in vitro and in vivo. Then, the optimal conditions for precision immunotherapy were further investigated to produce mild temperature (44 to 45 °C) accurately in tumor tissues. The optimal conditions with AuNR@SiO ₂ result in a distinct cell death with high early/late apoptosis and low necrosis, leading to very efficient ICD compared to lower or higher temperatures. In colon tumor-bearing mice, intratumorally injected AuNR@SiO ₂ efficiently promotes a mild temperature within the tumor tissues by local irradiation of near-infrared (NIR) laser. This mild PTT substantially increases the population of mature dendritic cells (DCs) and cytotoxic T cells (CTLs) within tumor tissues, ultimately reversing the ITM into an immune-responsive milieu. Furthermore, we found that the combination mild PTT with AuNR@SiO ₂ and anti-PD-L1 therapy could lead to the 100% complete regression of primary tumors and immunological memory to prevent tumor recurrence. Collectively, this study demonstrates that AuNR@SiO ₂ with a robust methodology capable of continuously inducing mild temperature accurately within the ITM holds promise as an approach to achieve the precision photothermal immunotherapy.