Receptor-mediated targeting of phthalocyanines to macrophages via covalentcoupling to native or maleylated bovine serum albumin

Targeted delivery of aluminum tetrasulfophthalocyanine (AIPcS(4)) to the sc avenger receptor of macrophages, via coupling to maleylated bovine serum al bumin (mal-BSA), was explored as a means to improve photodynamic efficacy. The AIPcS(4), was covalently coupled to BSA (9:1 molar ratio) via one or tw o sulfonamide-hexanoic-amide spacer chains, followed by treatment with male ic anhydride to yield the mal-BSA-phthalocyanine conjugates, The latter wer e tested for singlet oxygen production, receptor-mediated cell uptake and p hototoxicity toward J774 cells of macrophage origin and nonphagocytic EMT-6 cells. Cell uptake of I-125-mal-BSA showed specific binding for J774 cells but not for EMT-6 cells. Competition studies of the conjugates with I-125- mal-BSA showed that coupling of AlPcS4, to BSA resulted in recognition of t he conjugate by the scavenger receptor, whereas coupling to mal-BSA further enhanced its binding affinity. This suggests that affinity for the scaveng er receptor is related to the overall negative charge of the protein. Photo toxicity of the conjugates toward J774 cells paralleled their relative affi nity, with mal-BSA-AlPcS4, coupled via two spacer chains showing the highes t activity. The conjugates were less phototoxic toward the EMT-6 cell line. The activities in both cell lines of all conjugated AIPcS(4), preparations were, however, lower than that of the free disulfonated AIPcS(2). Possible implications for the in vivo use of protein-photosensitizer conjugates to target selectively various macrophage-associated disorders is discussed.