The pH in tumour cells and the tumour microenvironment has played important roles in cancer development and treatment.

No abstract

Immunogenic cancer cell death (ICD) is drawing worldwide attention as it allows dying cancer cells to regulate the host's anti-tumor immune system and awaken immunosurveillance. Thus, effectively activating therapy-induced ICD is of great clinical significance to raise systemic anti-tumor immunity and eradicate post-treatment/abscopal cancer tissues. Enhanced cytotoxic reactive oxygen species (ROS) generation in cancer therapy has been positively correlated to ICD induction, which inspires design of a therapy-induced ICD amplifier. The nanohybrid amplifier (FeOOH@STA/Cu-LDH) is devised based on Cu-containing layered double hydroxide (Cu-LDH), incorporating ROS inducer (FeOOH nanodots), ROS generation booster (Cu-LDH for photothermal therapy), and heat shock protein inhibitor (STA). Treating 4T1 tumor cells with this amplifier translocates calreticulins (CRT, one of main ICD signals) on the surface of dying cancer cells, which achieves the maximum at fever-type temperature (40-42 °C). To demonstrate immunotherapeutic efficacy of this nanohybrid, 4T1 tumor-bearing mouse model is established with primary and abscopal tumors. Significantly, only one treatment with the ICD amplifier eradicates the primary tumor and inhibits the abscopal tumor growth upon fever-type heating and induces more cytotoxic T lymphocytes in abscopal tumors and spleens after treatment for 1 week. This research thus provides a new insight into nanomaterial-mediated tumor immunotherapy.