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J Control Release. 2010 Nov 20;148(1):2-12. doi: 10.1016/j.jconrel.2010.06.008. Epub 2010 Jun 18.

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

Author information

1
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.
2
Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Norway.
3
PCI Biotech, Oslo, Norway.
4
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.

Abstract

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.

PMID:
20600406
DOI:
10.1016/j.jconrel.2010.06.008
[Indexed for MEDLINE]

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