CHAPTER 10: Photochemical Internalization – A Technology for Intracellular Drug Delivery: The Bleomycin Case
Published:15 Aug 2016
Special Collection: 2016 ebook collection
Cancer treatment is still mainly based on the three cornerstones: surgery, ionizing radiation and chemotherapy. Despite continuous improvements of clinical protocols, the mortality and morbidity after treatment of cancer is still very high. The low cure rates for many indications are not due to a lack of efficiency of current treatment regimens, but due to limited specificity, resulting in dose-limiting toxicity and side effects. This fact has paved way for the development of alternative treatment modalities that provide higher specificity for the target tissue, thus providing the opportunity to lower drug dosages and cause fewer side effects for the patients. One example is macromolecular-based therapies, which involve proteins (e.g. immunotoxins), DNA as in gene therapy (using viral and non-viral vectors and oligonucleotides) and nanoparticles used for the delivery of therapeutics. The utilization of macromolecules in the therapy of cancer and other diseases is becoming increasingly attractive. In particular, many monoclonal antibodies have received approval for clinical use. However, almost all approved macromolecular therapeutics target soluble factors or cell surface receptors, while those with intracellular targets have generally been found to exert limited therapeutic effects. This is due to the lack of efficient technologies for translocating macromolecules across cellular membranes, resulting in the accumulation and degradation of such therapeutics in endocytic vesicles. Photochemical internalization (PCI) is a novel technology that aims to circumvent this hurdle by promoting the release of endocytosed macromolecules into the cytosol. The PCI concept will here be described, with a major focus on the use of PCI in order to activate the therapeutic potential of the approved chemotherapeutic antibiotic bleomycin.