Receptor‐Mediated Targeting of Phthalocyanines to Macrophages Via Covalent Coupling to Native or Maleylated Bovine Serum Albumin

Abstract— Targeted delivery of aluminum tetrasulfophthalocyanine (AlPcS4) to the scavenger receptor of macrophages, via coupling to maleylated bovine serum albumin (mal‐BSA), was explored as a means to improve photodynamic efficacy. The AlPcS4 was covalently coupled to BSA (9:1 molar ratio) via one or two sulfonamide‐hexanoic‐amide spacer chains, followed by treatment with maleic anhydride to yield the mal‐BSA‐phthalocyanine conjugates. The latter were tested for singlet oxygen production, receptor‐mediated cell uptake and phototoxicity toward J774 cells of macrophage origin and nonphagocytic EMT‐6 cells. Cell uptake of 125I‐mal‐BSA showed specific binding for J774 cells but not for EMT‐6 cells. Competition studies of the conjugates with 125I‐mal‐BSA showed that coupling of AlPcS4 to BSA resulted in recognition of the conjugate by the scavenger receptor, whereas coupling to mal‐BSA further enhanced its binding affinity. This suggests that affinity for the scavenger receptor is related to the overall negative charge of the protein. Phototoxicity of the conjugates toward J774 cells paralleled their relative affinity, with mal‐BSA‐AlPcS4 coupled via two spacer chains showing the highest activity. The conjugates were less phototoxic toward the EMT‐6 cell line. The activities in both cell lines of all conjugated AlPcS4 preparations were, however, lower than that of the free disulfonated AlPcS2. Possible implications for the in vivo use of protein‐photosensitizer conjugates to target selectively various macrophage‐associated disorders is discussed.