Tumor-associated macrophage-targeted photodynamic cancer therapy using a dextran sulfate-based nano-photosensitizer.

The M2-like phenotype of tumor-associated macrophages (TAMs) present in tumors promotes tumor growth and metastasis. Therefore, targeting M2-like TAMs is a potential strategy for cancer therapy. Herein, we fabricated a dextran sulfate-based nano-photosensitizer (dextran sulfate-conjugated chlorin e6, DS-Ce6) to specifically target M2-like TAMs for enhanced photodynamic therapy (PDT). DS-Ce6 was preferentially taken up by interleukin-4-derived M2 macrophages, which overexpressed scavenger receptor-A and selectively targeted macrophages in co-cultured 4T1 tumors/macrophages. The nano-photosensitizer also effectively induced the apoptosis of tumor cells in both monolayer co-culture and three-dimensional co-culture spheroids of tumors/macrophages under laser irradiation. Moreover, the nano-photosensitizer specifically targeted F4/80 and CD206 double-positive M2-like TAMs within tumor tissues. Therefore, the specifically targeted delivery of DS-Ce6 to M2-like TAMs prominently induced tumor apoptosis, leading to excellent phototherapeutic effects in 4T1 tumor-bearing mice after PDT, suggesting the potential of DS-Ce6 for specific targeting of M2-like TAMs and enhanced PDT.