CpG-DNA loaded multifunctional MnO nanoshuttles for TLR9-specific cellular cargo delivery, selective immune-activation and MRI
Initiation of pathways that lead to a proliferation and chemoresistance by Toll-like receptors (TLRs) are an important factor in cancer progression. Multifunctional magnetic nanoparticles equipped with a pathogen-derived ligand (CpG) functioning as TLR agonists were used to show the impact of immune activation on human HNSCC (head and neck squamous cell carcinoma) cells. The response of human cancer cells to TLR signaling is linked to tumor biology. The magnetic MnO nanoparticles were coated with a multifunctional polymer, displaying no cytotoxicity and being able to enter cells while carrying foreign DNA (unmethylated CpG) to recognize intracellular TLR9. Both the particle and the nucleic acid were tagged with fluorescent markers for simultaneous visualization inside the cell. Cell and animal studies show that the multimodal nanoparticles used as a TLR carrier system allow monitoring simultaneously nanoparticle cellular trafficking and transport by optical and MRI imaging.