Introduction: Dendritic cells (DCs) are the professional antigen-presenting cells of the immune system. Currently, there are hundreds of ongoing clinical trials of DC based therapies for treatment of cancer, diabetes and other diseases. Efficient migration of vaccinated DCs to regional lymph nodes is very important for efficient stimulation of the immune system. However, monitoring of in vivo cell movement is not an easy job. Magnetic resonance imaging (MRI) is an imaging technique excellent for soft tissues with good biosafety. DCs labeled with MRI probes provides opportunity for one to track them dynamically. We have tested a few MRI probes and labeling strategies in previous studies, and were able to monitor labeled DCs migration to the draining lymph nodes.
Experimental Methods: MRI probes are based on nanocomposites of amphiphilic polymer/superparamagnetic iron oxide nanoparticle (SPION) clusters. Either polypeptide-polyester (such as poly(aspartic acid)-b-poly(ε-caprolactone)) or alkylated-polyelectrolyte (such as alkyl-PEI) polymers were chosen for wrapping of multiple SPIONs. Labeling of DC before and after maturation was compared to understand how the labeling process might have impacts on cell function and behaviors. MRI study was performed at different time points using a clinical 3 T scanner.
Results and Discussion: Either polypeptide-polyester or alkylated-polyelectrolyte polymer covered SPIONs were able to label DCs efficiently. We found that labeling of matured DCs have less effect on cell biomarker expression comparing to the labeling before maturation. The migration process of DCs in vivo was monitored by MRI. In TSE MR images, significant signal intensity reduction with time in central areas of lymph node after injection of labeled DCs into the footpad on the same side was observed. T2 values of central areas of the lymph node significantly reduced with time. Results indicated that labeled DCs migrated from footpad to the draining lymph node, leading to MRI signal intensity changes and T2 time reduction.
Conclusions: SPION-based MRI probes have efficient DC labeling capability and low cytotoxicity. DCs labeled with these polymer/SPION nanocomposites can migrate to the draining lymph nodes from the side of injection, and relative change of lymph node signal intensity and T2 value was observed under clinical MRI scanners.
The work was supported by National Key Basic Research Program of China (2013CB933903).
References:
[1] Wang D et al. Pharm Res 2014, 31; 1390-1406.
[2] Wu C et al. Adv Func Mater 2015, 25; 3581–3591.
[3] Xu Y et al. Biomaterials 2015, 58, 63-71.