Triple functional mild photothermal improves gene editing of PD-L1 for enhanced antitumor immunity

Traditional photothermal therapy ablates tumor cells by a high temperature (> 50 °C). Although it has shown good anti-tumor effect in animal models, the potential damages to healthy tissues and the unnecessary inflammatory reactions caused by the high temperature have hindered the clinical transitions of traditional photothermal therapy. In this study, we used polydopamine (PDA) as a mild photothermal material and control the maximum temperature below 45 °C, which not only avoided the side effects caused by a high temperature, but also ablated a fraction of tumor cells and produced tumor antigens. Meanwhile, the near-infrared (NIR) light also served as a “switch” to trigger the release of CRISPR/Cas9 RNP from Fe3O4 nanoparticles (Fe3O4 NPs) after their accumulation to tumor sites via magnetic targeting. The triple functional mild photothermal therapy achieved significant PD-L1 gene knockout efficiency in the tumor-bearing mice, reversed the condition of immunosuppression in the tumor microenvironment, led to a higher level of anti-tumor immune responses and effectively inhibited the growth of melanoma. We anticipate that this triple functional mild photothermal therapy would provide a potential new approach for the treatment of malignant tumors. [Display omitted] •Tumor targeted delivery of CRISPR/Cas9 RNP by mesoporous polydopamine coated Fe3O4 NPs.•Laser-triggered the responsive release of CRISPR/Cas9 RNP.•Triple functional mild photothermal therapy combined with gene editing effectively inhibited the growth of malignant tumor.•ICD effect and the knockdown of PD-L1 gene significantly enhanced the anti-tumor immune responses.