A CTL‐Inspired Killing System Using Ultralow‐Dose Chemical‐Drugs to Induce a Pyroptosis‐Mediated Antitumor Immune Function

Abstract

AbstractA Cytotoxic T lymphocyte‐inspired system capable of using ultralow‐dose chemical drugs to manipulate cell death is needed to investigate the antitumor immunotherapy. Recent studies reveal pyroptosis promotes antitumor immune function. However, high‐dose chemotherapy leads to cytokine release syndrome by pyroptosis. Therefore, pyroptosis‐inducing ultralow‐dose chemotherapy is potential in preclinical and clinical research, but its efficacy, safety, and the antitumor immune responses are not clear. Here, a near‐infrared light controllable killing system (BIK system) is established by which ultralow‐dose doxorubicin can be spatiotemporally transported to tumor cells and mediate efficient pyroptosis. This BIK system reduces total drug consumption to less than one‐thirtieth the common dose in vitro. Moreover, this BIK system exhibited good tumor targeting and tumor penetration. This system is applied for pyroptosis‐induced antitumor therapies, which shows less than ≈25 µg kg−1 doxorubicin is sufficient for tumor regression with negligible injuries to major organs. The antitumor immune function are proven to correlate with the impressive efficacy of pyroptosis‐inducing ultralow‐dose chemotherapy. This study provides new insights into the design of nanoassisted systems for activating the antitumor immunity by microstimulation; the application of the BIK system suggests that ultralow‐dose chemotherapy is sufficient for inducing a robust pyroptosis‐mediated antitumor immunity.