title: Photochemical disruption of endocytic vesicles before delivery of drugs: a new strategy for cancer therapy.
abstract: The development of methods for specific delivery of drugs is an important issue for many cancer therapy approaches. Most of macromolecular drugs are taken into the cell through endocytosis and, being unable to escape from endocytic vesicles, eventually are degraded there, which hinders their therapeutic usefulness. We have developed a method, called photochemical internalization, based on light-induced photochemical reactions, disrupting endocytic vesicles specifically within illuminated sites e.g. tumours. Here we present a new drug delivery concept based on photochemical internalization-principle -- photochemical disruption of endocytic vesicles before delivery of macromolecules, leading to an instant endosomal release instead of detrimental stay of the molecules in endocytic vesicles. Previously we have shown that illumination applied after the treatment with macromolecules substantially improved their biological effect both in vitro and in vivo. Here we demonstrate that exposure to light before delivery of protein toxin gelonin improves gelonin effect in vitro much more than light after. However, in vitro transfection with reporter genes delivered by non-viral and adenoviral vectors is increased more than 10- and six-fold, respectively, by both photochemical internalization strategies. The possible cellular mechanisms involved, and the potential of this new method for practical application of photochemical internalization concept in cancer therapy are discussed.
authors.affiliation: Department of Biophysics, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway. lina.prasmickaite@labmed.uio.no
authors.forename: L
authors.initials: L
authors.lastname: Prasmickaite
authors.forename: A
authors.initials: A
authors.lastname: Høgset
authors.forename: P K
authors.initials: PK
authors.lastname: Selbo
authors.forename: B Ø
authors.initials: BØ
authors.lastname: Engesaeter
authors.forename: M
authors.initials: M
authors.lastname: Hellum
authors.forename: K
authors.initials: K
authors.lastname: Berg
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D003911:Dextrans / Q000378:metabolism; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D011992:Endosomes / Q000502:physiology*; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008856:Microscopy, Fluorescence; D010778:Photochemotherapy; D010940:Plant Proteins / Q000627:therapeutic use*; D054789:Ribosome Inactivating Proteins, Type 1; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology; D013997:Time Factors; D014162:Transfection / Q000379:methods*; D022161:Transport Vesicles / Q000528:radiation effects*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003911:Dextrans; D008164:Luminescent Proteins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C015219:fluorescein isothiocyanate dextran; D049452:Green Fluorescent Proteins; C025674:GEL protein, Gelonium multiflorum; D016650:Fluorescein-5-isothiocyanate