Skip to main content

Photochemical Internalization: A Novel Technology for Targeted Macromolecule Therapy

  • Chapter
  • First Online:
  • 2207 Accesses

Abstract

Photochemical internalization (PCI) is a novel technology for release of endocytosed macromolecules into the cytosol. The technology is based on the use of photosensitizers located in endocytic vesicles that upon activation by light induces a release of macromolecules from their compartmentalization in endocytic vesicles. PCI has been shown to enhance the biological activity of a large variety of macromolecules and other molecules that do not readily penetrate the plasma membrane, including type I ribosome-inactivating proteins (RIPs), gene-encoding plasmids, adenovirus, oligonucleotides, and the chemotherapeuticum bleomycin. PCI has also been shown to enhance the treatment effect of targeted therapeutic macromolecules. The results show that PCI can induce efficient light-directed delivery of macromolecules into the cytosol, indicating that PCI may have a variety of useful applications for site-specific drug delivery, e.g., in gene therapy, vaccination, and cancer treatment. Our studies also indicate that PCI of bleomycin is superior to PDT in targeting the tumor periphery and that this is partly the cause of the improved treatment effect of PCI as compared to PDT.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Varkouhi AK, Scholte M, Storm G, Haisma HJ (2011) Endosomal escape pathways for delivery of biologicals. J Control Release 151:220–228

    Article  CAS  Google Scholar 

  2. Berg K, Selbo PK, Prasmickaite L, Tjelle TE, Kjølsrud S, Rodal GH, Anholt H, Sandvig K, Moan J, Gaudernack G, Fodstad Ø, Rodal SK, Høgset A (1999) Photochemical internalization. A novel technology for site-specific delivery of macromolecules into cytosol. Cancer Res 59:1180–1183

    CAS  Google Scholar 

  3. Selbo PK, Weyergang A, Høgset A, Norum OJ, Berstad MB, Vikdal M, Berg K (2010) Photochemical internalization provides time and space controlled endo-lysosomal escape of therapeutic molecules. J Control Release 148:2–12

    Article  CAS  Google Scholar 

  4. Berg K, Dietze A, Kaalhus O, Høgset A (2005) Site-specific drug delivery by photochemical internalization enhances the antitumor effect of bleomycin. Clin Cancer Res 11:8476–8485

    Article  CAS  Google Scholar 

  5. Høgset A, Prasmickaite L, Selbo PK, Hellum M, Engesæter BØ, Berg K (2004) Photochemical internalisation in drug and gene delivery. Adv Drug Deliv Res 56(1):95–115

    Article  Google Scholar 

  6. Berg K, Nordstrand S, Selbo PK, Tran DTT, Angell-Petersen E, Høgset A (2011) Disulfonated tetraphenyl chlorin (TPCS2a), a novel photosensitizer developed for clinical utilization of photochemical internalization. Photochem Photobiol Sci 10:1637–1651

    Google Scholar 

  7. Pron G, Mahrour N, Orlowski S, Tounekti O, Poddevin B, Belehradek J Jr, Mir LM (1999) Internalisation of the bleomycin molecules responsible for bleomycin toxicity: a receptor—mediated endocytosis mechanism. Biochem Pharmacol 57:45–56

    Article  CAS  Google Scholar 

  8. Poddevin B, Orlowski S, Belehradek Jr J, Mir LM (1991) Very high cytotoxicity of bleomycin introduced into the cytosol of cells in culture. Biochem Pharmacol 42:S67–67

    Google Scholar 

  9. Silve A, Leray I, Mir LM (2012) Demonstration of cell membrane permeabilization to medium-sized molecules caused by a single 10 ns electric pulse. Bioelectrochemistry 87:260–264

    Google Scholar 

  10. Selbo PK, Sivam G, Fodstad Ø, Sandvig K, Berg K (2001) In vivo documentation of photochemical internalization, a novel approach for site specific cancer therapy. Int J Cancer 92:761–766

    Article  CAS  Google Scholar 

  11. Pastan I, Hassan R, Fitzgerald DJ, Kreitman RJ (2006) Immunotoxin therapy of cancer. Nat Rev Cancer 6:559–565

    Article  CAS  Google Scholar 

  12. Selbo PK, Rosenblum MG, Cheung L, Zhang W, Berg K (2009) Multi-modality therapeutics with potent anti-tumor effects: photochemical internalization enhances delivery of the fusion toxin scFvMEL/rGel. PLoS ONE 4(8):e6691

    Article  Google Scholar 

  13. Clarke M, Collins R, Darby S et al (2005) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 366(9503):2087–2106

    CAS  Google Scholar 

  14. Norum O-J, Gaustad J-V, Angell-Petersen E, Rofstad1 EK, Peng Q, Giercksky KE, Berg K (2009) Photochemical internalization of bleomycin is superior to photodynamic therapy due to the therapeutic effect in the tumor periphery. Photochem Photobiol 85:740–49

    Google Scholar 

  15. Norum OJ, Giercksky KE, Berg K (2009) Photochemical internalization as an adjunct to marginal surgery in a human sarcoma model. Photochem Photobiol Sci 8:758–762

    Article  CAS  Google Scholar 

  16. Mohamedali KA, Kedar D, Sweeney P, Kamat A, Davis DW, Eve BY, Huang S, Thorpe PE, Dinney CP, Rosenblum MG (2005) The vascular-targeting fusion toxin VEGF121/rGel inhibits the growth of orthotopic human bladder carcinoma tumors. Neoplasia 7:912–920

    Article  CAS  Google Scholar 

  17. Abdel-Hady ES, Martin-Hirsch P, Duggan-Keen M, Stern PL, Moore JV, Corbitt G, Kitchener HC, Hampson IN (2001) Immunological and viral factors associated with the response of vulval intraepithelial neoplasia to photodynamic therapy. Cancer Res 61:192–196

    CAS  Google Scholar 

  18. Gollnick SO, Vaughan L, Henderson BW (2002) Generation of effective antitumor vaccines using photodynamic therapy. Cancer Res 62(6):1604–1608

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kristian Berg .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Berg, K., Weyergang, A., Vikdal, M., Norum, OJ., Selbo, P.K. (2014). Photochemical Internalization: A Novel Technology for Targeted Macromolecule Therapy. In: Abdel-Kader, M. (eds) Photodynamic Therapy. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-39629-8_6

Download citation

Publish with us

Policies and ethics