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Transformable Nanosensitizer with Tumor Microenvironment‐Activated Sonodynamic Process and Calcium Release for Enhanced Cancer Immunotherapy
Author(s) -
Tan Xuan,
Huang Jingzhao,
Wang Yiqian,
He Shasha,
Jia Le,
Zhu Yanhong,
Pu Kanyi,
Zhang Yan,
Yang Xiangliang
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202102703
Subject(s) - sonodynamic therapy , tumor microenvironment , cancer research , immunotherapy , immunogenic cell death , reactive oxygen species , cancer immunotherapy , chemistry , medicine , immune system , immunology , biochemistry , tumor cells
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 (TiO 2 @CaP) that reinvigorates ROS generation and dissolves its CaP shell to release Ca 2+ in an acidic tumor microenvironment (TME) under ultrasound activation. Thus, TiO 2 @CaP acts as a smart nanosonosensitizer that specifically induces mitochondrial dysfunction via overloading intracellular Ca 2+ ions to synergize with the sonodynamic process in the TME. TiO 2 @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), TiO 2 @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.