Low-density lipoprotein-bound aluminum sulfophthalocyanine: targeting tumor cells for photodynamic therapy

Abstract

The aim of this study was to evaluate the role of low-density lipoproteins (LDLs) as a vehicle for aluminum sulfophthalocyanine ( AlPcS ) to target tumor cells for photodynamic therapy (PDT). LDLs are biological particles containing an apolipoprotein which recognizes with high affinity specific receptors on many cell types, including cancer cells. LDL was loaded with AlPcS in two different manners. In the first procedure, the tetrasulfonated AlPcS 4 was covalently bound to the protein part of the LDL via amide bonds to 6-carboxypentylaminosulfonyl spacer chains attached to two of the four sulfonate groups, i.e. AlPcS 4 A 2 . In the second procedure, the AlPcS 4 was substituted with a linear dodecylaminosulfonyl chain, i.e. AlPcS 4 ( C 12 ) and non-covalently inserted into the phospholipid monolayer of the LDL. Both preparations contained over 50 moles AlPcS /mole LDL. They were tested in vitro for their phototoxic properties against the EMT-6 mouse mammary tumor cell line and the A-549 human lung adenocarcinoma cell line. Cell survival was assessed using the MTT colorimetric assay. Association of the free AlPcS 4 ( C 12 ) with LDL increased the in vitro phototoxicity of the dye substantially against both cell lines while the covalently loaded AlPcS 4 A 2 -LDL preparation showed little cytotoxicity, even at a 10-fold-higher light or drug doses. It was postulated that the covalent labeling of the protein moiety with the Pc greatly reduced LDL receptor recognition, rendering this derivative photo-inactive. Photodynamic therapy of EMT-6 tumor-bearing mice showed that the free and LDL-associated AlPcS 4 ( C 12 ) exhibited similar activities, with 100% cure one week post-PDT at 0.2 μmol kg −1 . We conclude that the attached aliphatic chain of the AlPcS 4 ( C 12 ) greatly enhances the phototoxicity of the parent AlPcS 4 but that pre-association of the AlPcS 4 ( C 12 ) with LDL does not further augment its in vivo photodynamic efficacy.