Fig. 5

Non-viral systemic NIS gene delivery strategies to glioblastoma (GBM). a (left panel) Potential approach to use synthetic polymers to deliver the theranostic NIS gene directly to GBM cells. (1) The polymer backbone is functionalized with ligands (targeting domain) that have a high affinity to cell surface receptors that are overexpressed in GBM cells. Polymers are loaded with NIS pDNA. (2) Following systemic administration of polymers, the pDNA is released to the GBM cells after binding of the polymer to the cell receptor. b (right panel) Mesenchymal stem cell (MSC)-based delivery of NIS targeting the tumor microenvironment of GBM. (1) MSCs can be easily isolated from patients from different tissue sources (e.g. bone marrow or adipose tissue) and (2) genetically modified with the NIS gene under the control of tumor-stroma specific gene promoters. (3) Engineered MSCs can be amplified in the laboratory and systemically administered back to the patient or over the allogenic barrier. Tumor-secreted factors (e.g. inflammatory cytokines) promote direct migration and extravasation of MSCs to GBM where they become part of the tumor stroma. NIS expression is induced after promoter activation. Following successful NIS gene transfer using both delivery platforms, diagnostic and therapeutic application of radioactive NIS substrates can be applied. pDNA; plasmid DNA