Nanosensitizer-mediated augmentation of sonodynamic therapy efficacy and antitumor immunity

Yongjiang Li, Wei Chen, Yong Kang, Xueyan Zhen, Zhuoming Zhou, Chuang Liu, Shuying Chen, Xiangang Huang, Hai-Jun Liu, Seyoung Koo, Na Kong, Xiaoyuan Ji, Tian Xie () and Wei Tao ()
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Yongjiang Li: Harvard Medical School
Wei Chen: Harvard Medical School
Yong Kang: Tianjin University
Xueyan Zhen: Harvard Medical School
Zhuoming Zhou: Harvard Medical School
Chuang Liu: Harvard Medical School
Shuying Chen: Harvard Medical School
Xiangang Huang: Harvard Medical School
Hai-Jun Liu: Harvard Medical School
Seyoung Koo: Harvard Medical School
Na Kong: Harvard Medical School
Xiaoyuan Ji: Tianjin University
Tian Xie: Hangzhou Normal University
Wei Tao: Harvard Medical School

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract The dense stroma of desmoplastic tumor limits nanotherapeutic penetration and hampers the antitumor immune response. Here, we report a denaturation-and-penetration strategy and the use of tin monosulfide nanoparticles (SnSNPs) as nano-sonosensitizers that can overcome the stromal barrier for the management of desmoplastic triple-negative breast cancer (TNBC). SnSNPs possess a narrow bandgap (1.18 eV), allowing for efficient electron (e−)-hole (h+) pair separation to generate reactive oxygen species under US activation. More importantly, SnSNPs display mild photothermal properties that can in situ denature tumor collagen and facilitate deep penetration into the tumor mass upon near-infrared irradiation. This approach significantly enhances sonodynamic therapy (SDT) by SnSNPs and boosts antitumor immunity. In mouse models of malignant TNBC and hepatocellular carcinoma (HCC), the combination of robust SDT and enhanced cytotoxic T lymphocyte infiltration achieves remarkable anti-tumor efficacy. This study presents an innovative approach to enhance SDT and antitumor immunity using the denaturation-and-penetration strategy, offering a potential combined sono-immunotherapy approach for the cancer nanomedicine field.

Date: 2023
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DOI: 10.1038/s41467-023-42509-7

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