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; Wei Tao

doi:10.1038/s41467-023-42509-7

Nanosensitizer-mediated augmentation of sonodynamic therapy efficacy and antitumor immunity

Nat Commun. 2023 Nov 1;14(1):6973. doi: 10.1038/s41467-023-42509-7.

Authors

Yongjiang Li^#¹, Wei Chen^#¹, Yong Kang², Xueyan Zhen¹, Zhuoming Zhou¹, Chuang Liu¹, Shuying Chen¹, Xiangang Huang¹, Hai-Jun Liu¹, Seyoung Koo¹, Na Kong^{1

3

4}, Xiaoyuan Ji^{2

4}, Tian Xie^{5

6

7

8}, Wei Tao⁹

Affiliations

¹ Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
² Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, 300072, Tianjin, China.
³ Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China.
⁴ School of Pharmacy, Hangzhou Normal University, 311121, Hangzhou, Zhejiang, China.
⁵ School of Pharmacy, Hangzhou Normal University, 311121, Hangzhou, Zhejiang, China. tianxie@hznu.edu.cn.
⁶ Key Laboratory of Element Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, 311121, Hangzhou, Zhejiang, China. tianxie@hznu.edu.cn.
⁷ Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, 311121, Hangzhou, Zhejiang, China. tianxie@hznu.edu.cn.
⁸ Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, 311121, Hangzhou, Zhejiang, China. tianxie@hznu.edu.cn.
⁹ Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. wtao@bwh.harvard.edu.

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carcinoma, Hepatocellular* / therapy
Cell Line, Tumor
Humans
Liver Neoplasms* / therapy
Mice
Nanoparticles* / therapeutic use
Neoplasms* / therapy
Reactive Oxygen Species
Triple Negative Breast Neoplasms* / therapy
Ultrasonic Therapy*

Substances

Reactive Oxygen Species