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Title: Transformable nanosensitizer with tumor microenvironment-activated sonodynamic process and calcium release for enhanced cancer immunotherapy
Authors: Tan, Xuan
Huang, Jingzhao
Wang, Yiqian
He, Shasha
Jia, Le
Zhu, Yanhong
Pu, Kanyi
Zhang, Yan
Yang, Xiangliang
Keywords: Engineering::Chemical engineering
Issue Date: 2021
Source: Tan, X., Huang, J., Wang, Y., He, S., Jia, L., Zhu, Y., Pu, K., Zhang, Y. & Yang, X. (2021). Transformable nanosensitizer with tumor microenvironment-activated sonodynamic process and calcium release for enhanced cancer immunotherapy. Angewandte Chemie International Edition, 60(25), 14051-14059.
Project: 2019-T1-002-045
Journal: Angewandte Chemie International Edition 
Abstract: Despite the promise of sonodynamic processes in cancer therapy, existing sonosensitizers often fail to regulate the generation of reactive oxygen species (ROS) against tumors, potentially leading to off-target toxicity to normal tissues. We report a transformable core-shell nanosonosensitizer (TiO2 @CaP) that reinvigorates ROS generation and dissolves its CaP shell to release Ca2+ in an acidic tumor microenvironment (TME) under ultrasound activation. Thus, TiO2 @CaP acts as a smart nanosonosensitizer that specifically induces mitochondrial dysfunction via overloading intracellular Ca2+ ions to synergize with the sonodynamic process in the TME. TiO2 @CaP substantially enhances immunogenic cell death, resulting in enhanced T-cell recruitment and infiltration into the immunogenic cold tumor (4T1). In conjunction with checkpoint blockade therapy (anti-PD 1), TiO2 @CaP-mediated sonodynamic therapy elicits systemic antitumor immunity, leading to regression of non-treated distant tumors and inhibition of lung metastasis. This work paves the way to development of "smart" TME-activatable sonosensitizers with temporospatial control over antitumor responses.
ISSN: 1433-7851
DOI: 10.1002/anie.202102703
Rights: © 2021 Wiley-VCH GmbH. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SCBE Journal Articles

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