Moreover, compared to the HNSCC xenograft nude mice model, the immune response, temperature of tumor surface after PTT and anti-tumor efficacy of Gel-N-ICG NPs were enhanced in Tgfbr1/Pten 2cKO head and neck carcinoma mice model which was of a closer TME to human HNSCC. This evidence concerns the gene PTEN and head and neck squamous cell carcinoma.