Photochemical internalisation in drug and gene delivery.

This article reviews a novel technology, named photochemical internalisation (PCI), for light-induced delivery of genes, proteins and many other classes of therapeutic molecules. Degradation of macromolecules in endocytic vesicles after uptake by endocytosis is a major intracellular barrier for the therapeutic application of macromolecules having intracellular targets of action. PCI is based upon the light activation of a drug (a photosensitizer) specifically locating in the membrane of endocytic vesicle inducing the rupture of this membrane upon illumination. Thereby endocytosed molecules can be released to reach their target of action before being degraded in lysosomes. The fact that this effect is induced by illumination means that the biological activity of the molecules can be activated at specific sites in the body, simply by illuminating the relevant region. We have used the PCI strategy to obtain light-induced delivery of a variety of molecules, including proteins, peptides, oligonucleotides, genes and low molecular weight drugs. In several cases, a >100-fold increase in biological activity has been observed.

[1]  J P Cooke,et al.  Photoangioplasty for Human Peripheral Atherosclerosis: Results of a Phase I Trial of Photodynamic Therapy With Motexafin Lutetium (Antrin) , 2000, Circulation.

[2]  I Rosenthal,et al.  PHTHALOCYANINES AS PHOTODYNAMIC SENSITIZERS * , 1991, Photochemistry and photobiology.

[3]  E. Keystone,et al.  Amelioration of antigen-induced arthritis in rabbits by induction of apoptosis of inflammatory cells with local application of transdermal photodynamic therapy. , 1998, Arthritis and rheumatism.

[4]  D. Scherman,et al.  A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[5]  K. Berg,et al.  Photochemical internalisation increases the cytotoxic effect of the immunotoxin MOC31‐gelonin , 2000, International journal of cancer.

[6]  G. Kroemer,et al.  Apoptosis induction by the photosensitizer verteporfin: identification of mitochondrial adenine nucleotide translocator as a critical target. , 2001, Cancer research.

[7]  L. Barbieri,et al.  Ribosome-inactivating proteins from plants. , 1993, Biochimica et Biophysica Acta.

[8]  A. Moor,et al.  The photodecontamination of cellular blood components: mechanisms and use of photosensitization in transfusion medicine. , 1996, Transfusion medicine reviews.

[9]  K. Berg,et al.  Evaluation of Different Photosensitizers for Use in Photochemical Gene Transfection¶ , 2001, Photochemistry and photobiology.

[10]  F. Stirpe,et al.  Gelonin, a new inhibitor of protein synthesis, nontoxic to intact cells. Isolation, characterization, and preparation of cytotoxic complexes with concanavalin A. , 1980, The Journal of biological chemistry.

[11]  K. König,et al.  Photodynamic therapy in psoriasis: suppression of cytokine production in vitro and recording of fluorescence modification during treatment in vivo , 2004, Archives of Dermatological Research.

[12]  C. Regillo Update on photodynamic therapy. , 2000, Current opinion in ophthalmology.

[13]  J Moan,et al.  PHOTOCHEMOTHERAPY OF CANCER: EXPERIMENTAL RESEARCH , 1992, Photochemistry and photobiology.

[14]  P. Ghosh,et al.  Interaction of gelonin with macrophages: effect of lysosomotropic amines. , 1992, Experimental cell research.

[15]  C. Plank,et al.  Application of membrane-active peptides for drug and gene delivery across cellular membranes. , 1998, Advanced drug delivery reviews.

[16]  K. Berg,et al.  THE PHOTODEGRADATION OF PORPHYRINS IN CELLS CAN BE USED TO ESTIMATE THE LIFETIME OF SINGLET OXYGEN , 1991, Photochemistry and photobiology.

[17]  H. Pass,et al.  Photodynamic therapy in oncology: mechanisms and clinical use. , 1993, Journal of the National Cancer Institute.

[18]  Kristian Berg,et al.  In vivo documentation of photochemical internalization, a novel approach to site specific cancer therapy , 2001, International journal of cancer.

[19]  K. Berg,et al.  Transgene expression is increased by photochemically mediated transduction of polycation-complexed adenoviruses , 2004, Gene Therapy.

[20]  K. Berg,et al.  Photochemical transfection: a new technology for light-induced, site-directed gene delivery. , 2000, Human gene therapy.

[21]  J Moan,et al.  INTRACELLULAR LOCALIZATION OF SULFONATED meso‐TETRAPHENYLPORPHINES IN A HUMAN CARCINOMA CELL LINE * , 1990, Photochemistry and photobiology.

[22]  Kristian Berg,et al.  Light-induced adenovirus gene transfer, an efficient and specific gene delivery technology for cancer gene therapy , 2002, Cancer Gene Therapy.

[23]  K Mechtler,et al.  The size of DNA/transferrin-PEI complexes is an important factor for gene expression in cultured cells , 1998, Gene Therapy.

[24]  J Moan,et al.  Oxygen dependence of the photosensitizing effect of hematoporphyrin derivative in NHIK 3025 cells. , 1985, Cancer research.

[25]  D. Lane,et al.  Cellular delivery of impermeable effector molecules in the form of conjugates with peptides capable of mediating membrane translocation. , 2001, Bioconjugate chemistry.

[26]  A. Moor,et al.  Photodynamic sterilization of red cells and its effect on contaminating white cells: viability and mechanism of cell death , 1999, Transfusion.

[27]  N. Oleinick,et al.  Mutagenicity of Photodynamic Therapy as Compared to UVC and Ionizing Radiation in Human and Murine Lymphoblast Cell Lines , 1997, Photochemistry and photobiology.

[28]  J. Newman,et al.  Photodynamic therapy of viral contaminants with potential for blood banking applications , 1988, Transfusion.

[29]  B. Davidson,et al.  Complexes of Adenovirus with Polycationic Polymers and Cationic Lipids Increase the Efficiency of Gene Transfer in Vitro and in Vivo* , 1997, The Journal of Biological Chemistry.

[30]  S. Agrawal,et al.  Antisense and/or immunostimulatory oligonucleotide therapeutics. , 2001, Current cancer drug targets.

[31]  A. Nixon Phage display as a tool for protease ligand discovery. , 2002, Current pharmaceutical biotechnology.

[32]  J Moan,et al.  Intracellular localization of photosensitizers. , 1989, Ciba Foundation symposium.

[33]  K. Berg,et al.  Sulfonated aluminium phthalocyanines as sensitizers for photochemotherapy. Effects of small light doses on localization, dye fluorescence and photosensitivity in V79 cells , 1994, International journal of cancer.

[34]  K. Berg,et al.  Release of gelonin from endosomes and lysosomes to cytosol by photochemical internalization. , 2000, Biochimica et biophysica acta.

[35]  G. Stables,et al.  Improved response of plaque psoriasis after multiple treatments with topical 5-aminolaevulinic acid photodynamic therapy. , 1999, Acta dermato-venereologica.

[36]  K. Berg,et al.  Photochemical disruption of endocytic vesicles before delivery of drugs: a new strategy for cancer therapy , 2002, British Journal of Cancer.

[37]  J D Waterfield,et al.  Photodynamic therapy; a comparison with other immunomodulatory treatments of adjuvant‐enhanced arthritis in MRL‐lpr mice , 1994, Clinical and experimental immunology.

[38]  M. Jung,et al.  Inhibitors of histone deacetylase as new anticancer agents. , 2001, Current medicinal chemistry.

[39]  Ari Helenius,et al.  Stepwise dismantling of adenovirus 2 during entry into cells , 1993, Cell.

[40]  Allen Cm,et al.  Role of activated oxygen species in photodynamic therapy. , 2000 .

[41]  D. Phillips,et al.  Kinetic and equilibrium studies of incorporation of di-sulfonated aluminum phthalocyanine into unilamellar vesicles. , 1999, Biochimica et biophysica acta.

[42]  Tayyaba Hasan,et al.  Photodynamic Treatment of Rheumatoid and Inflammatory Arthritis , 1996, Photochemistry and photobiology.

[43]  Q. Peng,et al.  Correlation of distribution of sulphonated aluminium phthalocyanines with their photodynamic effect in tumour and skin of mice bearing CaD2 mammary carcinoma. , 1995, British Journal of Cancer.

[44]  U. Schmidt-Erfurth,et al.  Mechanisms of action of photodynamic therapy with verteporfin for the treatment of age-related macular degeneration. , 2000, Survey of ophthalmology.

[45]  Inder M. Verma,et al.  Gene therapy: trials and tribulations , 2000, Nature Reviews Genetics.

[46]  I. Kirby,et al.  Adenovirus type 5 uptake by lung adenocarcinoma cells in culture correlates with Ad5 fibre binding is mediated by αvβ1 integrin and can be modulated by changes in β1 integrin function , 2001, The journal of gene medicine.

[47]  K. Tsurugi,et al.  The site of action of six different ribosome-inactivating proteins from plants on eukaryotic ribosomes: the RNA N-glycosidase activity of the proteins. , 1988, Biochemical and biophysical research communications.

[48]  G. LaMuraglia,et al.  Photodynamic therapy induces apoptosis in intimal hyperplastic arteries. , 2000, The American journal of pathology.

[49]  I. Tannock,et al.  A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer , 2000, Nature Medicine.

[50]  M. Wu Enhancement of immunotoxin activity using chemical and biological reagents. , 1997, British Journal of Cancer.

[51]  P. Robbins Gene therapy protocols , 1996 .

[52]  A. Urtti,et al.  Cell membranes as barriers for the use of antisense therapeutic agents. , 2002, Mini reviews in medicinal chemistry.

[53]  T. Dougherty,et al.  HOW DOES PHOTODYNAMIC THERAPY WORK? , 1992, Photochemistry and photobiology.

[54]  Kendric C. Smith,et al.  Topics In Photomedicine , 1984 .

[55]  K. Berg,et al.  Photochemical Transfection: A Technology for Efficient Light-Directed Gene Delivery , 2002, Somatic cell and molecular genetics.

[56]  G. Mælandsmo,et al.  Light directed gene transfer by photochemical internalisation. , 2003, Current gene therapy.

[57]  Kristian Berg,et al.  Photochemical internalization of a peptide nucleic acid targeting the catalytic subunit of human telomerase. , 2003, Cancer research.

[58]  J. Schneider,et al.  Hematoporphyrin uptake in atherosclerotic plaques: therapeutic potentials. , 1988, Neurosurgery.

[59]  A. S. Sobolev,et al.  Targeted intracellular delivery of photosensitizers to enhance photodynamic efficiency , 2000, Immunology and cell biology.

[60]  H Anholt,et al.  Photochemical internalization: a novel technology for delivery of macromolecules into cytosol. , 1999, Cancer research.

[61]  B. Epe,et al.  Oxidative DNA base damage induced by singlet oxygen and photosensitization: recognition by repair endonucleases and mutagenicity. , 2000, Mutation research.

[62]  J Moan,et al.  Lysosomes as photochemical targets , 1994, International journal of cancer.

[63]  W. Cheong,et al.  Photoangioplasty: An emerging clinical cardiovascular role for photodynamic therapy. , 2000, Circulation.

[64]  C. Pournaras,et al.  Principles of treatment of choroidal neovascularization with photodynamic therapy in age-related macular degeneration. , 1999, Seminars in ophthalmology.

[65]  R. Ward,et al.  Application of phage display technology to cancer research. , 2002, Current pharmaceutical biotechnology.

[66]  R. Crystal,et al.  Fiber Swap between Adenovirus Subgroups B and C Alters Intracellular Trafficking of Adenovirus Gene Transfer Vectors , 1999, Journal of Virology.

[67]  I. Kochevar,et al.  [2] Photosensitized production of singlet oxygen , 2000 .

[68]  D. McDonald,et al.  Coxsackie and adenovirus receptor (CAR)-dependent and major histocompatibility complex (MHC) class I-independent uptake of recombinant adenoviruses into human tumour cells , 1999, Gene Therapy.

[69]  M. Korbelik,et al.  Photodynamic therapy-mediated immune response against subcutaneous mouse tumors. , 1999, Cancer research.

[70]  G. Powis,et al.  A multisample assay for inhibitors of phosphatidylinositol phospholipase C: identification of naturally occurring peptide inhibitors with antiproliferative activity. , 1994, Anti-cancer drug design.

[71]  T J Dougherty,et al.  Identification of singlet oxygen as the cytotoxic agent in photoinactivation of a murine tumor. , 1976, Cancer research.

[72]  L. Mir,et al.  Internalisation of the bleomycin molecules responsible for bleomycin toxicity: a receptor-mediated endocytosis mechanism. , 1999, Biochemical pharmacology.

[73]  A. Fischer,et al.  Gene therapy of severe combined immunodeficiencies , 2002, Nature Reviews Immunology.

[74]  K. Berg,et al.  CELLULAR UPTAKE AND RELATIVE EFFICIENCY IN CELL INACTIVATION BY PHOTO ACTIVATED SULFONATED meso‐TETRAPHENYLPORPHINES , 1990, Photochemistry and photobiology.

[75]  T J Flotte,et al.  Photodynamic therapy of arteries. A novel approach for treatment of experimental intimal hyperplasia. , 1992, Circulation.

[76]  A. Mountain,et al.  Gene therapy: the first decade. , 2000, Trends in biotechnology.

[77]  D. Scheinberg,et al.  Immunotoxin resistance in multidrug resistant cells. , 2003, Cancer research.

[78]  A. Yamaguchi,et al.  Reduction of Vein Graft Disease Using Photodynamic Therapy with Motexafin Lutetium in a Rodent Isograft Model , 2000, Circulation.

[79]  N. Hackett,et al.  Fluorescent virions: dynamic tracking of the pathway of adenoviral gene transfer vectors in living cells. , 1998, Human gene therapy.

[80]  Bertrand Tavitian,et al.  Nucleic acid aptamers in cancer medicine , 2002, FEBS letters.

[81]  L. Mir,et al.  Bleomycin: revival of an old drug. , 1996, General pharmacology.