Liposome-based nanocomplexes with pH-sensitive second near-infrared photothermal property for combinational immunotherapy

Natural killer (NK) cell-mediated immunotherapy has shown a great promise for treatments of tumors, while some strategies that can improve its therapeutic efficacy and reduce potential adverse events are highly desired. We herein report a pH-sensitive second near-infrared (NIR-II) photothermal liposomal nanocomplex for enhanced NK cell-based immunotherapy of breast cancer. Such nanocomplex (LNCDS) consists of charge-transfer nanoparticles (CTN) with pH-sensitive NIR-II photothermal effect, deoxyribonuclease I (DNase I), NK cell stimulant (SIS3) and a surface coated thermal-responsive liposome shell. Upon 1064 nm laser irradiation, LNCDS generates mild heat in a controlled manner, which results in destruction of thermal-responsive liposome shell to allow on-demand release of stimulants and DNase I in tumor sites. The released DNase I not only kills cancer cells, but also induces immunogenic cell death (ICD), which synergizes with the action of the released SIS3 to promote activation of NK cells and cytotoxic T lymphocytes, contributing to enhanced therapeutic efficacy of immunotherapy. As a result, a single treatment of LNCDS upon NIR-II photoactivation greatly inhibits the growths of subcutaneously implanted primary and distant tumors in a breast cancer murine model, and even completely prevents lung metastasis. This study thus offers a photo-controlled drug delivery nanosystem for efficacy and precise NK cell-mediated immunotherapy of cancer.