CHAPTER 9: Photochemical Internalization-Enhanced Targeting of Vasculature and Cancer Stem Cells—Present and Future Perspectives

In this review, we present recent developments in photochemical internalization (PCI) technology as a rational strategy for the specific and efficient targeting of vasculature and cancer stem cells. The PCI method is based on the same principles as photodynamic therapy; however, the major difference is the coadministration of a drug that co-localizes with the PCI photosensitizer in endocytic vesicles (endosomes and lysosomes). In addition, the photosensitizer needs to be primarily located in the membranes of the endocytic vesicles and the drug to be activated by PCI has to be trapped inside the endocytic vesicles. Photochemical-induced disruption of the membranes of these vesicles induces endosomal release of the drug of interest, thereby strongly enhancing its biological effect. Recently, we have demonstrated in various publications that the PCI method can be used for the targeting and rapid shutdown of the tumor vasculature, eradication of cancer stem cells and to enhance vaccines. Future PCI will be dependent on collaboration with academic or industry laboratories that have potent drugs that require improved endosomal escape. Currently, we are developing recombinant toxin-based therapeutics for better tumor cell and vasculature targeting.