Photochemical Internalization: From Bench to Bedside with a Novel Technology for Targeted Macromolecule Therapy

Authored by: Kristian Berg , Anette Weyergang , Anders Høgset , Pål K. Selbo

Handbook Ofphotomedicine

Print publication date:  October  2013
Online publication date:  October  2013

Print ISBN: 9781439884690
eBook ISBN: 9781439884706
Adobe ISBN:

10.1201/b15582-42

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Abstract

The utilization of macromolecules in the therapy of cancer and other diseases is becoming increasingly relevant to successful tumor therapy. Recent advances in molecular biology and biotechnology have made it possible to improve the targeting and design of cytotoxic agents, DNA complexes, and other macromolecules for clinical applications. To achieve the expected biological effect of these macromolecules, in many cases, internalization to the cell cytosol is crucial. Macromolecules are frequently prohibited from penetrating cell membranes, but are instead endocytosed and without any active intervention become degraded by hydrolytic enzymes in the lysosomes. Thus, at an intracellular level, the most fundamental obstruction for cytosolic localization of therapeutic macromolecules is the membrane barrier of the endocytic vesicles (Varkouhi et al. 2010). Photo-Chemical internalization (PCI) is a novel technology for release of endocytosed macromolecules into the cytosol. PCI has been shown to potentiate the biological activity of a large variety of macromolecules and other molecules that do not readily penetrate the plasma membrane (Berg et al. 1999; Selbo et al. 2010). PCI may therefore be utilized for treatment of most solid tumors, and the first phase I/II clinical trial with PCI of bleomycin (Berg et al. 2005) for several cancer indications has recently been completed. This review will describe the mechanistic basis for the PCI technology, the present status, the potential clinical advantages, and future perspectives.

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