Photochemical internalization (PCI) is a photodynamic therapy-based approach for improving the delivery of
macromolecules and genes into the cell cytosol. Prodrug activating gene therapy (suicide gene therapy) employing
the transduction of the E. coli cytosine deaminase (CD) gene into tumor cells, is a promising method. Expression of
this gene within the target cell produces an enzyme that converts the nontoxic prodrug, 5-FC, to the toxic metabolite,
5-fluorouracil (5-FU). 5-FC may be particularly suitable for brain tumors, because it can readily cross the bloodbrain
barrier (BBB). In addition the bystander effect, where activated drug is exported from the transfected cancer
cells into the tumor microenvironment, plays an important role by inhibiting growth of adjacent tumor cells.
Tumor-associated macrophages (TAMs) are frequently found in and around glioblastomas. Monocytes or
macrophages (Ma) loaded with drugs, nanoparticles or photosensitizers could therefore be used to target tumors by
local synthesis of chemo attractive factors. The basic concept is to combine PCI, to enhance the ex vivo transfection
of a suicide gene into Ma, employing specially designed core/shell NP as gene carrier.