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.

Date Published: 10 March 2015
PDF: 6 pages
Proc. SPIE 9305, Optical Techniques in Neurosurgery, Neurophotonics, and Optogenetics II, 93050C (10 March 2015); doi: 10.1117/12.2082590

Published in SPIE Proceedings Vol. 9305:
Optical Techniques in Neurosurgery, Neurophotonics, and Optogenetics II
Henry Hirschberg M.D.; E. Duco Jansen; Samarendra K. Mohanty; Nitish V. Thakor; Qingming Luo; Steen J. Madsen, Editor(s)