Chloroaluminum phthalocyanine tetrasulfonate delivered via acid-labile diplasmenylcholine-folate liposomes: intracellular localization and synergistic phototoxicity.

Abstract

Folate-diplasmenylcholine (1,2-di-O-(Z-1'-hexadecenyl)-sn-glycero-3-phosphocholine; DPPlsC) liposomes have been shown to greatly enhance the potency of water-soluble antitumor agents via a selective folate-mediated uptake and acid-catalyzed endosomal escape mechanism (Rui et al. J. Am. Chem. Soc., 1998; 120:11213--18). This study describes an adaptation of this strategy for the delivery of chloroaluminum phthalocyanine tetrasulfonate ([AlPcS(4)](4-)), a water-soluble sensitizer used in photodynamic therapy, in a binary targeting scheme designed to enhance both its tumor selectivity and phototoxicity. [AlPcS(4)](4-)/DPPlsC:folate liposomes (9.8 microM bulk concentration, 2.5 mM intraliposomal concentration) were substantially more phototoxic to folate-deficient KB cells than 12.5 microM free [AlPcS(4)](4-) after a 30 min irradiation (630-910 nm). Considerable differences in phototoxicity were observed, however, between the commercially-available AlPcS(4)(4-) and an HPLC purified sample of [AlPcS(4)](4-) due to an increased tendency for the latter to aggregate. Experiments with [AlPcS(4)](4-)/DPPC:folate and folate-free [AlPcS(4)](4-)/DPPlsC liposomes (acid-insensitive and non-targeted controls, respectively) showed significantly reduced phototoxicities under the same illumination conditions. Our results imply that higher concentrations of water-soluble sensitizers can be delivered to target cells using the folate receptor-mediated pathway, which can change both the biodistribution and intracellular localization of the sensitizer when acid-labile DPPlsC liposomes are used as the delivery vehicle. Potential advantages of this approach include the use of lower bulk [AlPcS(4)](4-) concentrations, rapid plasma clearance of free [AlPcS(4)](4-), and better phototoxic responses, due to higher intracellular [AlPcS(4)](4-) concentrations combined with reduced collateral photodamage arising from misguided sensitizer accumulation, thereby enhancing the selective phototoxicity of PDT treatments.

• Authors: M M Qualls, D H Thompson
• Journal: International journal of cancer (Int J Cancer) Vol. 93 Issue 3 Pg. 384-92 (Aug 01 2001) ISSN: 0020-7136 [Print] United States
• PMID: 11433404 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2001 Wiley-Liss, Inc.

Chemical References

• Drug Carriers
• Indoles
• Liposomes
• Organometallic Compounds
• Photosensitizing Agents
• Plasmalogens
• Tetrazolium Salts
• Thiazoles
• choline plasmalogens
• chloroaluminum tetrasulfophthalocyanine
• Folic Acid
• Aluminum
• Luciferases
• thiazolyl blue

Topics

• Aluminum
• Biological Transport (drug effects)
• Cell Survival (drug effects, radiation effects)
• Dermatitis, Phototoxic
• Drug Carriers
• Drug Delivery Systems
• Folic Acid (chemistry)
• Humans
• Indoles (administration & dosage, metabolism)
• KB Cells (drug effects, metabolism, radiation effects)
• Liposomes
• Luciferases (metabolism)
• Microscopy, Confocal
• Molecular Structure
• Organometallic Compounds (administration & dosage, metabolism)
• Photochemotherapy
• Photosensitizing Agents (administration & dosage, metabolism)
• Plasmalogens (chemistry)
• Tetrazolium Salts (metabolism)
• Thiazoles (metabolism)