The possible role of ionic species in selective biodistribution of photochemotherapeutic agents toward neoplastic tissue.
Photochemotherapeutic agents are photosensitizers that are selectively retained by neoplastic tissue. When tumor tissue containing these drugs is irradiated with visible electromagnetic radiation, the photosensitizing reaction may lead to tumor eradication, termed photodynamic therapy. Exogenous photosensitizers commonly used in clinical trials are mainly porphyrin derivatives. Phthalocyanines are currently being investigated as "second generation" photochemotherapeutic agents. The mechanism by which these photosensitizers are selectively retained in neoplastic tissue is unclear. This review examines the role of tissue and cellular pH as a factor in selective biodistribution. The pH values of normal and tumor tissue are summarized and the ionic species distribution diagram of porphyrins is presented. A two-fold mechanism of selective biodistribution is advanced, one involving normal tissue vs. tumor tissue selectivity, the other involving intracellular vs. intercellular distribution of sensitizer ionic species.
Pottier
R
R
Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, Ontario.
Kennedy
J C
JC
D000818:Animals; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000493:pharmacokinetics; D007477:Ions; D054833:Isoindoles; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010778:Photochemotherapy; D011166:Porphyrins / Q000493:pharmacokinetics; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D007211:Indoles; D007477:Ions; D054833:Isoindoles; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C013647:phthalocyanine