Antitumor Effects of a Distinct Sonodynamic Nanosystem through Enhanced Induction of Immunogenic Cell Death and Ferroptosis with Modulation of Tumor Microenvironment

Yuan, Haitao1,2; Ma, Jingbo1,2; Huang, Wei3; Gong, Ping4; Shi, Fei5; Xu, Xiaolong1,2; Fu, Chunjin6,7; Wang, Xiaoxian8; Wong, Yin Kwan9; Long, Ying8; Sun, Xin1,2; Li, Weihua10; Li, Zhijie1,2; Wang, Jigang1,2,6,7

2023-05-01

10.1021/jacsau.3c00156

JACS AU   影响因子和分区

2691-3704

Sonodynamic therapy (SDT) holds great promise to be applied for cancer therapy in clinical settings. However, its poor therapeutic efficacy has limited its applications owing to the apoptosis-resistant mechanism of cancer cells. Moreover, the hypoxic and immunosuppressive tumor microenvironment (TME) also weakens the efficacy of immunotherapy in solid tumors. Therefore, reversing TME remains a formidable challenge. To circumvent these critical issues, we developed an ultrasound-augmented strategy to regulate the TME by utilizing an HMME-based liposomal nanosystem (HB liposomes), which can synergistically promote the induction of ferroptosis/apoptosis/immunogenic cell death (ICD) and initiate the reprograming of TME. The RNA sequencing analysis demonstrated that apoptosis, hypoxia factors, and redox-related pathways were modulated during the treatment with HB liposomes under ultrasound irradiation. The in vivo photo acoustic imaging experiment showed that HB liposomes enhanced oxygen production in the TME, alleviated TME hypoxia, and helped to overcome the hypoxia of the solid tumors, consequently improving the SDT efficiency. More importantly, HB liposomes extensively induced ICD, resulting in enhanced T-cell recruitment and infiltration, which normalizes the immunosuppressive TME and facilitates antitumor immune responses. Meanwhile, the HB liposomal SDT system combined with PD1 immune checkpoint inhibitor achieves superior synergistic cancer inhibition. Both in vitro and in vivo results indicate that the HB liposomes act as a sonodynamic immune adjuvant that is able to induce ferroptosis/ apoptosis/ICD via generated lipid-reactive oxide species during the SDT and reprogram TME due to ICD induction. This sonodynamic nanosystem integrating oxygen supply, reactive oxygen species generation, and induction of ferroptosis/apoptosis/ICD is an excellent strategy for effective TME modulation and efficient tumor therapy.

sonodynamic therapy immunogenic cell death ferroptosis cancer therapy

ESCI

英语

第一 ; 通讯

Shenzhen Science and Technology Innovation Commission[JCYJ20200109120205924] ; GuangDong Basic and Applied Basic Research Foundation[2022A1515110745] ; International Science and Technology Cooperation for Shenzhen Technol- ogy Innovation Plan[GJHZ20200731095411034] ; National Key Research and Development Program of China["2020YFA0908000","2022YFC2303600"] ; Chinese Postdoctoral Science Foundation[2022M712190] ; Shenzhen Science and Technology Innovation Committee (SZSTI)[RCYX20221008092950121] ; Science and Technology Foundation of Shenzhen[JCYJ20210324115800001] ; Shenzhen Fund for Guangdong Provincial High -level Clinical Key Specialties[SZGSP001] ; Shenzhen Governmental Sustainable Development Fund[KCXFZ20201221173612034] ; Shenzhen key Laboratory of Kidney Diseases[ZDSYS201504301616234]

Chemistry

Chemistry, Multidisciplinary

WOS:000984423400001

AMER CHEMICAL SOC

Web of Science

1.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Dept Cardiol,Shenzhen Cardiovasc Minimally Invas M, Shenzhen 518020, Guangdong, Peoples R China
2.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Shenzhen Clin Res Ctr Geriatr, Shenzhen 518020, Guangdong, Peoples R China
3.Sun Yat Sen Univ, Sch Chem Engn & Technol, Zhuhai 519082, Peoples R China
4.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Dept Emergency, Shenzhen 518020, Guangdong, Peoples R China
5.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Dept Infect Dis, Shenzhen 518020, Guangdong, Peoples R China
6.China Acad Chinese Med Sci, Artemisinin Res Ctr, Beijing 100700, Peoples R China
7.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China
8.Southern Univ Sci & Technol, Peoples Hosp, Affiliated Hosp 1, Dept Hyperbar Oxygen Med, Shenzhen 518020, Guangdong, Peoples R China
9.Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117600, Singapore
10.Shenzhen Univ, Shenzhen Peoples Hosp 2, Affiliated Hosp 1, Hlth Sci Ctr,Med Imaging Dept, Shenzhen 518035, Peoples R China

Yuan, Haitao,Ma, Jingbo,Huang, Wei,et al. Antitumor Effects of a Distinct Sonodynamic Nanosystem through Enhanced Induction of Immunogenic Cell Death and Ferroptosis with Modulation of Tumor Microenvironment[J]. JACS AU,2023,3(5).

Yuan, Haitao.,Ma, Jingbo.,Huang, Wei.,Gong, Ping.,Shi, Fei.,...&Wang, Jigang.(2023).Antitumor Effects of a Distinct Sonodynamic Nanosystem through Enhanced Induction of Immunogenic Cell Death and Ferroptosis with Modulation of Tumor Microenvironment.JACS AU,3(5).

Yuan, Haitao,et al."Antitumor Effects of a Distinct Sonodynamic Nanosystem through Enhanced Induction of Immunogenic Cell Death and Ferroptosis with Modulation of Tumor Microenvironment".JACS AU 3.5(2023).