Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 93, Issue 3, Pages 384-392Publisher
WILEY
DOI: 10.1002/ijc.1339
Keywords
acid-sensitive liposome; chloroaluminum phthalocyanine tetrasulfonate; diplasmenylcholine; drug delivery; drug targeting; photodynamic therapy; photooxidation; receptor-mediated endocytosis
Categories
Funding
- NIDCR NIH HHS [R01 DE13030] Funding Source: Medline
- NIGMS NIH HHS [F31 GM18546, R01 GM55266] Funding Source: Medline
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Folate-diplasmenylcholine (1,2-di-O-(Z-1 ' -hexadecenyl)sn-glycero-3-phosphocholine; DPPIsC) 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 ol, i, Am. Chem, Sec., 1998; 120:11213-18). This study describes an adaptation of this strategy for the delivery of chloroaluminum phthalocyanine tetrasulfonate (AlPcS44-), a water-soluble sensitizer used in photodynamic therapy, in a binary targeting scheme designed to enhance both its tumor selectivity and phototoxicity, AlPcS44-/DPPIsC:folate liposomes (9.8 muM bulk concentration, 2.5 mM intraliposomal concentration) were substantially more phototoxic to folate-deficient KB cells than 12.5 muM free AlPcS44- after a 30 min irradiation (630-910 nm), Considerable differences in phototoxicity were observed however, between the commercially-available AlPcS44- and an HPLC purified sample of AlPcS44- due to an increased tendency for the latter to aggregate. Experiments with AlPcS44-/DPPC:folate and folate-free AlPcS44-/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 AlPcS44- concentrations, rapid plasma clearance of free AlPcS44-, and better phototoxic responses, due to higher intracellular AlPcS44- concentrations combined with reduced collateral photodamage arising from misguided sensitizer accumulation, thereby enhancing the selective phototoxicity of PDT treatments. (C) 2001 Wiley-Liss, Inc .
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