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

Weyergang, Anette; Selbo, Pål Kristian; Berg, Kristian

doi:10.1016/j.jconrel.2005.12.002

Cited by 71 publications

(66 citation statements)

References 181 publications

(199 reference statements)

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“…Several targeting methods are under development, such as the use of antibodies and derivatives thereof, receptor ligands, peptides, tissue-specific promoters and replication. Some targeting principles have been evaluated in combinations with PCI, such as immunotoxins [76], transferrin-and epidermal growth factor-conjugated vectors [29,[77][78][79] and protein affinity-toxins [80], transferrin-polylysin vector [29] and RGD sequences for integrin-targeting [47]. These results indicate that PCI can be used in combination with other targeting principles to further improve therapeutic specificity.…”

Section: Targeting and Specificitymentioning

confidence: 99%

Photochemical Internalization: A New Tool for Drug Delivery

Berg

Folini

Prasmickaite³

et al. 2007

CPB

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The utilisation of macromolecules in the therapy of cancer and other diseases is becoming increasingly important. Recent advances in molecular biology and biotechnology have made it possible to improve targeting and design of cytotoxic agents, DNA complexes and other macromolecules for clinical applications. In many cases the targets of macromolecular therapeutics are intracellular. However, 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. Photochemical internalisation (PCI) is a novel technology for the release of endocytosed macromolecules into the cytosol. The technology is based on the activation by light of photosensitizers located in endocytic vesicles to induce the release of macromolecules from the endocytic vesicles. Thereby, endocytosed molecules can be released to reach their target of action before being degraded in lysosomes. PCI has been shown to stimulate intracellular delivery of a large variety of macromolecules and other molecules that do not readily penetrate the plasma membrane, including type I ribosome-inactivating proteins (RIPs), DNA delivered as gene-encoding plasmids or by means of adenovirus or adeno-associated virus, peptide nucleic acids (PNAs) and chemotherapeutic agents such as bleomycin and in some cases doxorubicin. PCI of PNA may be of particular importance due to the low therapeutic efficacy of PNA in the absence of an efficient delivery technology and the 10-100-fold increased efficacy in combination with PCI. The efficacy and specificity of PCI of macromolecular therapeutics has been improved by combining the macromolecules with targeting moieties, such as the epidermal growth factor. In general, PCI can induce efficient light-directed delivery of macromolecules into the cytosol, indicating that it may have a variety of useful applications for site-specific drug delivery as for example in gene therapy, vaccination and cancer treatment.

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Section: Targeting and Specificitymentioning

confidence: 99%

Photochemical Internalization: A New Tool for Drug Delivery

Berg

Folini

Prasmickaite³

et al. 2007

CPB

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123

100

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“…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. These agents generally are not able to reach their intracellular target site efficiently, due to lack of capability to pass cellular membranes and/or the occurrence of degradation within endocytic vesicles.…”

Section: Efficacy Studiesmentioning

confidence: 99%

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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“…Epidermal growth factor (EGF) receptor (EGFR) is a widely used receptor for targeted delivery of anticancer therapeutics due to its overexpression in a large variety of tumors. PCI of EGFR-directed proteins toxins has been shown very promising both by using EGF and the monoclonal antibody cetuximab as targeting ligands (9,10). PCI can be considered as a multimodality therapy of photodynamic therapy (PDT; treatment with photosensitizers and light) and treatment with the macromolecule of interest (Fig.…”

Section: Introductionmentioning

confidence: 99%

Photodynamic therapy with an endocytically located photosensitizer cause a rapid activation of the mitogen-activated protein kinases extracellular signal-regulated kinase, p38, and c-Jun NH2 terminal kinase with opposing effects on cell survival

Weyergang

Kaalhus

Berg

2008

Molecular Cancer Therapeutics

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Photochemical internalization (PCI) is a method for release of endosomally/lysosomally trapped drugs into the cell cytosol. PCI is based on photosensitizers that accumulate in the membranes of endosomes and lysosomes. Light exposure generates reactive oxygen species that cause membrane rupture and subsequently drug release. PCI can be considered as a combination therapy of photodynamic therapy (PDT) and the administrated drug. The present work reports on mitogen-activated protein kinase signaling after PDT with the endocytically located photosensitizer TPPS 2a

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

Cited by 71 publications

References 181 publications

Photochemical Internalization: A New Tool for Drug Delivery

Photochemical Internalization: A New Tool for Drug Delivery

Cytosolic Delivery of Liposomally Targeted Proteins Induced by Photochemical Internalization

Photodynamic therapy with an endocytically located photosensitizer cause a rapid activation of the mitogen-activated protein kinases extracellular signal-regulated kinase, p38, and c-Jun NH2 terminal kinase with opposing effects on cell survival

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