Molecular Engineering‐Boosted High‐Performance AIE Sonosensitizer for Cancer Sonodynamic‐Augmented Immunotherapy

ABSTRACT Immunogenic cell death (ICD) has been demonstrated as a reliable approach to improve therapeutic effect in cancer treatment by triggering antitumor immunity. However, the trigger of ICD on the basis of chemotherapy and phototherapy meets the obstacles of serious side effect and poor penetration ability, which seriously impedes the therapeutic effect. The development of sonodynamic immunotherapy with the evoking of ICD presents high promise for cancer treatment with high efficacy. Herein, high performance aggregation‐induced emission (AIE) sonosensitizer is constructed on the basis of the engineering structure modulation for sonodynamic‐augmented immunotherapy. By regulating the intermolecular interaction and pull‐push electronic effect, sonosensitizer bearing AIE feature and amplified sono‐sensitizing effect is developed. In addition, in vitro observation demonstrated that thiolate‐substituted segment incorporation endows the molecules with enhanced cellular uptake efficiency and improved tumor cell eradication ability. More importantly, the developed sonosensitizer could efficiently evoke ICD upon the trigger of ultrasound, which allows for the efficient tumor eradication both at cellular level and in solid tumor. The inhibition of primary tumor and further boost systemic immunity response with the complete elimination toward the distant tumor is achieved. The investigation highlights the promise of utilizing AIE sonosensitizers in sonodynamic immunotherapy to conquer the current limitation of immunotherapy in solid tumor treatment.