Photochemical internalization provides time- and space-controlled endolysosomal escape of therapeutic molecules

• Published in: Journal of controlled release Vol. 148; no. 1; pp. 2 - 12
• Main Authors: Selbo, Pål Kristian, Weyergang, Anette, Høgset, Anders, Norum, Ole-Jacob, Berstad, Maria Brandal, Vikdal, Marie, Berg, Kristian
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.11.2010
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Cell Line, Tumor; Cell Survival - drug effects; Delayed-Action Preparations; Doxorubicin - pharmacology; Drug delivery; Drug Resistance, Multiple; Endocytosis; Endosomes - metabolism; Gene delivery; Lysosomes - metabolism; Mice; Mice, Inbred BALB C; Neoplasms - drug therapy; Photochemical internalization; Photochemical Processes; Photochemotherapy; Photodynamic therapy; Photosensitizing Agents - metabolism; Targeting; Xenograft Model Antitumor Assays; Gene delivery; Drug delivery; Photodynamic therapy; Targeting; Photochemical internalization
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2010.06.008

A successful cure of cancer by biopharmaceuticals with intracellular targets is dependent on both specific and sufficient delivery of the drug to the cytosol or nuclei of malignant cells. However, cytosolic delivery and efficacy of membrane-impermeable cancer therapeutics are often hampered by the sequestration and degradation of the drugs in the endolysosomal compartments. Hence, we developed photochemical internalization (PCI) as a site-specific drug delivery technology, which bursts the membrane of endocytic vesicles inducing release of entrapped drugs to the cytosol of light exposed cells. The principle of PCI has been demonstrated in >80 different cell lines and 10 different xenograft models of various cancers in different laboratories demonstrating its broad application potential. PCI-induced endosomal escape of protein- or nucleic acid-based therapeutics and some chemotherapeutics will be presented in this review. With a joint effort by life scientists the PCI technology is currently in a Phase I/II clinical trial with very promising initial results in the treatment of solid tumors. [Display omitted]