Molecular Engineering-Boosted High-Performance 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 based on 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 based on 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 towards 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.