Photochemical internalization provides time- and space-controlled endolysosomal escape of therapeutic molecules.
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.
Selbo
Pål Kristian
PK
Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Norway; PCI Biotech, Oslo, Norway. Electronic address: selbo@rr-research.no.
Weyergang
Anette
A
Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Norway.
Høgset
Anders
A
PCI Biotech, Oslo, Norway.
Norum
Ole-Jacob
OJ
Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Norway; Deparment of Surgical Oncology, Norwegian Radium Hospital, Oslo University Hospital, Norway.
Berstad
Maria Brandal
MB
Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Norway.
Vikdal
Marie
M
Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Norway.
Berg
Kristian
K
Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Norway.
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy*; D055668:Photochemical Processes; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D017319:Photosensitizing Agents; D004317:Doxorubicin