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The scientific basis of photochemical internalization (PCI) (Conference Presentation)
Author(s): Kristian Berg

Paper Abstract

The short lifetime and thereby the diffusion length of singlet oxygen as well as the correlation between photosensitizer (PS) fluorescence and treatment effects made it attractive in the 80-ties to analyze the intracellular localization of PSs to reveal the initial intracellular hit in PDT. Some PSs were found intracellularly in fluorescing granules that was found to be lysosomes and endosomes. Such vesicles were rupture upon exposure of the cells to light and the PS relocated to other compartments in the cells. About 40 different hydrolytic enzymes are found in late endosomes and lysosomes. Release of lysosomal hydrolases into cytosol has been documented to be a cytotoxic event. This suicide sac hypothesis originally postulated by De Duve suggests that released hydrolases lead to degradation of cellular constituents to such an extent that cellular functions are impaired and the cells subsequently die. However, it was found that a large fraction of the vesicles containing PSs could be ruptured without inducing substantial cytotoxicity. The scientific basis for this surprising observation as well as the potential utilization of the photochemical rupture of endosomes and lysosomes for intracellular delivery of various therapeutics, named photochemical internalization (PCI), will be discussed. During the last 20-30 years macromolecular therapeutics have become increasingly attractive for treatment of cancer due to their improved specificity and reduced side effects. Intracellular delivery of macromolecular therapeutics has however so far showed only limited success, a limitation that may be circumvented by PCI. The historic and scientific basis for PCI will be presented.

Paper Details

Date Published: 14 August 2019
PDF
Proc. SPIE 11070, 17th International Photodynamic Association World Congress, 110703A (14 August 2019); doi: 10.1117/12.2527907
Show Author Affiliations
Kristian Berg, Oslo Univ. Hospital (Norway)


Published in SPIE Proceedings Vol. 11070:
17th International Photodynamic Association World Congress
Tayyaba Hasan, Editor(s)

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