Alginate-zinc (II) phthalocyanine conjugates: Synthesis, characterization and tumor-associated macrophages-targeted photodynamic therapy

Tumor-associated macrophages (TAMs)-targeted photodynamic therapy (PDT) has dual-selectivity and hence is promising in cancer treatment. Since the scavenger receptor-A (SR-A) on TAMs can recognize polyanions, two molecular-weight sodium alginates (SA1, 41.2 kDa; SA2, 1231.5 kDa) were herein respectively conjugated with 1-[4-(2-aminoethyl) phenoxy] zinc (II) phthalocyanine (1) and two novel conjugates were obtained, characterized and evaluated for their TAMs-targeted PDT efficacy. The SA introduction makes 1 water-soluble, less aggregated and capable of emitting considerable fluorescence in water. Compared with 1, both conjugates, especially 1-SA1, can give higher selectivity and photocytotoxicity to SR-A-positive macrophages J774A.1 than SR-A-negative HepG2 cells. The in vivo biodistribution evaluation shows both conjugates can selectively accumulate at the tumor site and 1-SA1 owns higher tumor accumulation. 1-SA1 can achieve an 87 % tumor inhibition rate without observable systemic toxicity. These results reveal the great potential of SA as a carrier for conjugating anti-tumor drugs and 1-SA1 for TAMs-targeted PDT.