DSPE-PEG-IR780@MgAl-LDH nanoplatform for NIR-triggered antitumor activity and immune modulation in HNSCC

Head and neck squamous cell carcinoma (HNSCC) remain challenging to treat because of its invasiveness and frequent recurrence. This study investigated DSPE-PEG-IR780@MgAl-LDH as a nanoplatform for near-infrared (NIR)-triggered antitumor activity and associated immune modulation. The preparation was characterized by electron microscopy, dynamic light scattering, and spectroscopic analyses, and its photothermal behavior and biological effects were evaluated in FaDu cells and immunocompetent mice bearing MOC1 tumors. DSPE-PEG-IR780@MgAl-LDH exhibited NIR absorption, concentration-dependent heating, and reproducible thermal responses during repeated irradiation-cooling cycles. Under 808-nm irradiation at 1 W/cm², treatment reduced FaDu cell viability and increased apoptosis, accompanied by enhanced intracellular DCF fluorescence, mitochondrial membrane depolarization, and reduced HSP90 protein abundance. Compared with free IR780, DSPE-PEG-IR780@MgAl-LDH produced stronger tumor-associated fluorescence and more persistent circulating fluorescence. In vivo, DSPE-PEG-IR780@MgAl-LDH combined with irradiation achieved the greatest tumor growth inhibition among the tested groups, with reduced Ki-67 staining and increased TUNEL positivity. These effects were accompanied by increased proportions of CD80⁺CD86⁺ cells in draining lymph nodes and CD3⁺CD8a⁺ cells in tumors, together with elevated serum IFN-γ and TNF-α levels. Body weight, serum biochemical indices, and major-organ histology indicated no overt systemic toxicity during the observation period. These findings support the potential of DSPE-PEG-IR780@MgAl-LDH for NIR-triggered tumor treatment accompanied by immune-associated changes in HNSCC models.