Chlorin-Based Photoactivable Galectin-3-Inhibitor Nanoliposome for Enhanced Photodynamic Therapy and NK Cell-Related Immunity in Melanoma

Photodynamic therapy (PDT) is an encouraging alternative therapy for melanoma treatment and Ce6-mediated PDT has shown some exciting results in clinical trials. However, PDT in melanoma treatment is still hampered by some melanoma's protective mechanisms like antiapoptosis mechanisms and treatment escape pathways. Combined therapy and enhancing immune stimulation were proposed as effective strategies to overcome this resistance. In this paper, a Chlorin-based photoactivable Galectin-3-inhibitor nanoliposome (PGIL) was designed for enhanced Melanoma PDT and immune activation of Natural Killer (NK) cells. PGIL were synthesized by encapsulating the photosensitizer chlorin e6 and low molecular citrus pectin in the nanoliposome to realize NIR-triggered PDT and low molecular citrus pectin (LCP) release into the cytoplasm. The intracellular release of LCP inhibits the activity of galectin-3, which increases the apoptosis, inhibits the invade ability, and enhances the recognition ability of Natural Killer (NK) cells to tumor cells in melanoma cells after PDT. These effects of PGIL were tested in cells and nude mice, and the mechanisms during the in vivo treatment were preliminarily studied. The results showed that PGIL can be an effective prodrug for melanoma therapy.