Photochemical internalisation: a novel drug delivery system.
The present report reviews a number of recently published papers on a novel technology for the cytosolic delivery of macromolecules named photochemical internalisation (PCI). PCI is based upon the light activation of a drug (a photosensitizer) specifically located in the membrane of endocytic vesicles. Light which is absorbed by the photosensitizer induces the formation of reactive oxygen species, of which singlet oxygen ((1)O(2)) is the predominant form. Singlet oxygen oxidizes biomolecules in the membranes of endosomes and lysosomes, resulting in a subsequent release of the contents of these compartments into the cytosol. Photosensitizers have a higher affinity for tumour tissues than for most normal tissues and are used in photodynamic therapy of various types of cancers. We have taken advantage of the PCI strategy to enhance the delivery of a variety of macromolecules, including ribosome-inactivating toxins, an immunotoxin, horse radish peroxidase, a ras peptide, RNA, oligonucleotides and protein encoding DNA, to the cytosol. Normally, a major intracellular barrier to the application of therapeutically interesting peptides and proteins or the application of DNA and RNA in gene therapy is the degradation of the macromolecules in the endocytic vesicles after uptake by endocytosis. Therefore, a photochemically induced rupture of endocytic vesicles and the subsequent cytosolic release of the macromolecules aids these molecules in escaping attack by the lysosomal hydrolases, thereby maintaining their biological activity. Thus, PCI represents a novel principle for the cytosolic delivery of biologically active macromolecules which overcomes the pivotal intracellular barrier of endosomes and lysosomes. In addition to being utilised as a new site-specific cancer therapy method, PCI can also be applied as a research tool for macromolecule delivery both in vitro and in vivo.
Selbo
Pål Kristian
PK
Department of Biophysics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo, Norway. p.k.selbo@labmed.uio.no
Høgset
Anders
A
Prasmickaite
Lina
L
Berg
Kristian
K
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000528:radiation effects; D003600:Cytosol / Q000378:metabolism; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects / Q000528:radiation effects; D011992:Endosomes / Q000187:drug effects / Q000528:radiation effects* / Q000648:ultrastructure; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000528:radiation effects; D015316:Genetic Therapy / Q000379:methods; D018796:Immunoconjugates / Q000008:administration & dosage / Q000493:pharmacokinetics; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000528:radiation effects; D007425:Intracellular Membranes / Q000187:drug effects / Q000528:radiation effects*; D008247:Lysosomes / Q000187:drug effects / Q000528:radiation effects* / Q000648:ultrastructure; D051379:Mice; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000528:radiation effects; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000528:radiation effects; D010940:Plant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011166:Porphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000528:radiation effects; D011506:Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D017382:Reactive Oxygen Species; D054789:Ribosome Inactivating Proteins, Type 1; D012270:Ribosomes / Q000187:drug effects; D026082:Singlet Oxygen; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D018796:Immunoconjugates; D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D010940:Plant Proteins; D011166:Porphyrins; D011506:Proteins; D017382:Reactive Oxygen Species; D054789:Ribosome Inactivating Proteins, Type 1; D026082:Singlet Oxygen; C064331:aluminum phthalocyanine disulfonate; C025674:GEL protein, Gelonium multiflorum