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Photochemical internalisation: a novel drug delivery system
Pål Kristian Selbo1, Anders Høgset, Lina Prasmickaite
1Department of Biophysics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo, Norway. p.k.selbo@labmed.uio.no
Summary
Photochemical internalisation (PCI) uses light-activated photosensitizers to release macromolecules into the cytosol. This novel technology enhances drug delivery by overcoming endosomal barriers, improving therapeutic potential.
Area of Science:
- Biotechnology
- Cell Biology
- Drug Delivery
Background:
- Macromolecule delivery into the cytosol faces intracellular barriers, primarily degradation within endosomes and lysosomes.
- Photochemical internalisation (PCI) is a novel technology designed to overcome these barriers for enhanced cytosolic delivery.
- Photosensitizers, used in cancer therapy, can be localized to endocytic vesicle membranes for light-activated release.
Purpose of the Study:
- To review and highlight the potential of photochemical internalisation (PCI) as a technology for cytosolic delivery of macromolecules.
- To discuss the mechanism of PCI, involving light activation of photosensitizers and subsequent endosomal/lysosomal escape.
- To explore the application of PCI for delivering various macromolecules, including toxins, peptides, RNA, and DNA, for therapeutic and research purposes.
Main Methods:
- Review of recently published literature on photochemical internalisation (PCI).
- Description of the mechanism: light activation of photosensitizers within endocytic vesicles to generate reactive oxygen species (e.g., singlet oxygen).
- Oxidation of vesicle membranes leading to rupture and release of macromolecule contents into the cytosol.
Main Results:
- PCI successfully enhances the cytosolic delivery of diverse macromolecules like toxins, peptides, RNA, and DNA.
- The strategy circumvents the degradation of macromolecules by lysosomal hydrolases, preserving biological activity.
- Photosensitizers' preferential accumulation in tumor tissues suggests potential for site-specific cancer therapy.
Conclusions:
- Photochemical internalisation (PCI) offers a novel and effective principle for overcoming the intracellular barrier of endosomes and lysosomes for macromolecule delivery.
- PCI facilitates the cytosolic release of biologically active macromolecules, maintaining their integrity and function.
- This technology holds promise for both site-specific cancer therapy and as a research tool for in vitro and in vivo macromolecule delivery studies.