Release of gelonin from endosomes and lysosomes to cytosol by photochemical internalization

Selbo, Pål Kristian

doi:10.1016/s0304-4165(00)00082-9

Cited by 76 publications

(81 citation statements)

References 30 publications

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“…A general trend can be observed: the longer the illumination time, the stronger the cytotoxic effect. This observation corresponds to observations done by others using PCI in combination with the plant toxin gelonin (21,23). Routinely, we used 75 s as illumination time in our experiments.…”

Section: Effect Of Illumination Timesupporting

confidence: 85%

“…Selbo et al demonstrated that the use of PCI enhanced the potency of the plant toxin gelonin in inhibiting cellular protein synthesis by a factor of 300 (21). In addition, the low-molecular weight drug bleomycin (22), antigenic peptides (23), immunotoxins (24,25), peptide nucleic acids (26) and even colloidal carriers for gene delivery (27)(28)(29) have been successfully delivered into the cytosol via PCI.…”

Section: Efficacy Studiesmentioning

confidence: 99%

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Cytosolic Delivery of Liposomally Targeted Proteins Induced by Photochemical Internalization

et al. 2007

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Purpose. The application of therapeutic proteins is often hampered by limited cell entrance and lysosomal degradation, as intracellular targets are not reached. By encapsulation of proteins into targeted liposomes, cellular uptake via endocytosis can be enhanced. To prevent subsequent lysosomal degradation and promote endosomal escape, photochemical internalization (PCI) was studied here as a tool to enhance endosomal escape. PCI makes use of photosensitising agents which localize in endocytic vesicles, inducing endosomal release upon light exposure. Materials and Methods. The cytotoxic protein saporin was encapsulated in different types of targeted liposomes. Human ovarian carcinoma cells were incubated with the photosensitiser TPPS2a and liposomes. To achieve photochemical internalization, the cells were illuminated for various time periods. Cell viability was used as read-out. Illumination time and amount of encapsulated proteins were varied to investigate the influence of these parameters. Results. The cytotoxic effect of liposomally targeted saporin was enhanced by applying PCI, likely due to enhanced endosomal escape. The cytotoxic effect was dependent on the amount of encapsulated saporin and the illumination time. Conclusion. PCI is a promising technique for promoting cytosolic delivery of liposomally targeted saporin. PCI may also be applicable to other liposomally targeted therapeutic proteins with intracellular targets.

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Section: Effect Of Illumination Timesupporting

confidence: 85%

Section: Efficacy Studiesmentioning

confidence: 99%

Cytosolic Delivery of Liposomally Targeted Proteins Induced by Photochemical Internalization

et al. 2007

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“…PCI has been shown to increase the cytosolic delivery and subsequent therapeutic effect in vitro of many macromolecules such as proteins (Selbo et al 2000a, Dietze et al 2003, immunotoxins (Selbo et al 2000b, Selbo et al 2001a and DNA delivered by cationic polymers , Prasmickaite et al 2001, adenovirus , Engesaeter et al 2005, Engesaeter et al 2006a, Engesaeter et al 2006b) and adenoassociated virus . PCI in vitro has also been reported as an intracellular delivery system for peptides (Berg et al 1996, Berg et al 1999, PNAs (Shiraishi & Nielsen 2006, siRNA (Oliveira et al 2007) and some chemotherapeutics, such as bleomycin , doxorubicin , Lai et al 2007) and mitoxantrone (Adigbli et al 2007).…”

Section: Pci Of Different Classes Of Moleculesmentioning

confidence: 99%

“…The endocytic trafficking of EGFR has also been shown to differ dependent on EGF-or cetuximabstimulation (Roepstorff et al 2008). This could also influence on the PCI induced toxicity of the two targeting toxins as the effect of PCI may be dependent on the type of endocytic vesicle from which the toxin is to be released (Selbo et al 2000a). The incubation time for the two toxin conjugates were, however, different in the two papers (4 hrs for EGF-saporin and 18 hrs for cetuximab-saporin), and the two targeted toxins must be evaluated under the same experimental conditions to confirm the difference in PCI mediated toxicity.…”

Section: Egf Versus Cetuximab As a Targeting Ligandmentioning

confidence: 99%

Photochemically stimulated drug delivery increases the cytotoxicity and specificity of EGF–saporin

Weyergang

Selbo

Berg

2006

Journal of Controlled Release

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“…Although a powerful inhibitor of protein synthesis in cell-free systems, it has low toxicity in intact cells and or in vivo (Barbieri and Stirpe, 1982;Scott et al, 1987). Gelonin localised in the same intracellular compartments as the photosensitiser disulphonated aluminium phthalocyanine (Selbo et al, 2000); the latter has been shown to localise within endocytic vesicles both in vitro (Moan et al, 1989) and in vivo (Høgset et al, 2004). Illumination of cells containing the two agents resulted in drug release into the cytoplasm (Høgset et al, 2004).…”

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confidence: 99%

Photochemical internalisation of chemotherapy potentiates killing of multidrug-resistant breast and bladder cancer cells

et al. 2007

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Multidrug resistance (MDR) is the major confounding factor in adjuvant solid tumour chemotherapy. Increasing intracellular amounts of chemotherapeutics to circumvent MDR may be achieved by a novel delivery method, photochemical internalisation (PCI). PCI consists of the co-administration of drug and photosensitiser; upon light activation the latter induces intracellular release of organellebound drug. We investigated whether co-administration of hypericin (photosensitiser) with mitoxantrone (MTZ, chemotherapeutic) plus illumination potentiates cytotoxicity in MDR cancer cells. We mapped the extent of intracellular co-localisation of drug/ photosensitiser. We determined whether PCI altered drug-excreting efflux pump P-glycoprotein (Pgp) expression or function in MDR cells. Bladder and breast cancer cells and their Pgp-overexpressing MDR subclones (MGHU1, MGHU1/R, MCF-7, MCF-7/R) were given hypericin/MTZ combinations, with/without blue-light illumination. Pilot experiments determined appropriate sublethal doses for each. Viability was determined by the 3-[4,5-dimethylthiazolyl]-2,5-diphenyltetrazolium bromide assay. Intracellular localisation was mapped by confocal microscopy. Pgp expression was detected by immunofluorescence and Pgp function investigated by Rhodamine123 efflux on confocal microscopy. MTZ alone (0.1 -0.2 mg ml À1 ) killed up to 89% of drug-sensitive cells; MDR cells exhibited less cytotoxicity (6 -28%). Hypericin (0.1 -0.2 mM) effects were similar for all cells; light illumination caused none or minimal toxicity. In combination, MTZ /hypericin plus illumination, potentiated MDR cell killing, vs hypericin or MTZ alone. (MGHU1/R: 38.65 and 36.63% increase, Po0.05; MCF-7/R: 80.2 and 46.1% increase, Po0.001). Illumination of combined MTZ/hypericin increased killing by 28.15% (Po0.05 MGHU1/R) compared to dark controls. Intracytoplasmic vesicular co-localisation of MTZ/hypericin was evident before illumination and at serial times post-illumination. MTZ was always found in sensitive cell nuclei, but not in dark resistant cell nuclei. In illuminated resistant cells there was some mobilisation of MTZ into the nucleus. Pgp expression remained unchanged, regardless of drug exposure. Pgp efflux was blocked by the Pgp inhibitor verapamil (positive control) but not impeded by hypericin. The increased killing of MDR cancer cells demonstrated is consistent with PCI. PCI is a promising technique for enhancing treatment efficacy.

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Release of gelonin from endosomes and lysosomes to cytosol by photochemical internalization

Cited by 76 publications

References 30 publications

Cytosolic Delivery of Liposomally Targeted Proteins Induced by Photochemical Internalization

Cytosolic Delivery of Liposomally Targeted Proteins Induced by Photochemical Internalization

Photochemically stimulated drug delivery increases the cytotoxicity and specificity of EGF–saporin

Photochemical internalisation of chemotherapy potentiates killing of multidrug-resistant breast and bladder cancer cells

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