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  3. Enhancement of antitumor immunotherapy using mitochondria-targeted cancer cell membrane-biomimetic MOF-mediated sonodynamic therapy and checkpoint blockade immunotherapy

Enhancement of antitumor immunotherapy using mitochondria-targeted cancer cell membrane-biomimetic MOF-mediated sonodynamic therapy and checkpoint blockade immunotherapy

  • J Nanobiotechnology. 2022 May 14;20(1):228. doi: 10.1186/s12951-022-01453-2.
Jiali Luo  # 1 2,  Xue Wang  # 1 2,  Zhan Shi 1 2,  Yiqing Zeng 1 2,  Liangcan He 3,  Jing Cao 1 2,  Yu Sun 1 2,  Tao Zhang 4 5,  Pintong Huang 6 7
Affiliations

Affiliations

  • 1 Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, No. 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, People's Republic of China.
  • 2 Research Center of Ultrasound in Medicine and Biomedical Engineering, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, No. 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, People's Republic of China.
  • 3 School of Medicine and Health, Harbin Institute of Technology, Harbin, 150080, People's Republic of China.
  • 4 Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, No. 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, People's Republic of China. zhangtao-us@zju.edu.cn.
  • 5 Research Center of Ultrasound in Medicine and Biomedical Engineering, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, No. 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, People's Republic of China. zhangtao-us@zju.edu.cn.
  • 6 Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, No. 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, People's Republic of China. huangpintong@zju.edu.cn.
  • 7 Research Center of Ultrasound in Medicine and Biomedical Engineering, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, No. 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, People's Republic of China. huangpintong@zju.edu.cn.
  • # Contributed equally.
PMID: 35568916 DOI: 10.1186/s12951-022-01453-2
Abstract

Immunotherapeutic interventions represent a promising approach to treating Cancer, with strategies such as immune checkpoint blockade (ICB), immunogenic sonodynamic therapy (SDT), and immune Adjuvant T cell delivery having exhibited clinical promise. In this report, we describe the use of Cancer cell membrane-coated triphenylphosphonium (TPP) decorated nano-metal-organic framework (nMOF) constructs [Zr-TCPP(TPP)/R837@M] that were used to generate homologous, mitochondria-targeted platforms with a high rate of sonosensitizer loading. This construct was utilized to simultaneously promote tumor antigen presentation via enhancing SDT while synergistically promoting dendritic cell (DC) maturation through the delivery of the Toll-like Receptor agonist R837. In vitro, these functionalized nMOFs were readily internalized by homologous tumor cells in which they were efficiently targeted to the mitochondria, promoting DC activation through the induction of immunogenic cell death (ICD) following ultrasound exposure. Moreover, this nanoplatform was able to achieve in vivo synergy with anti-CTLA-4 ICB to reverse immunosuppression tumor microenvironment (TME), thus achieving more robust antitumor efficacy capable of suppressing metastatic disease progression and facilitating the development of durable antitumor memory responses. Together, these results highlight a promising approach to achieving enhanced SDT activity while overcoming an immunosuppressive TME, thereby achieving more robust antitumor immunity.

Keywords

Cancer cell membrane; Immunotherapy; Metal–organic frameworks; Mitochondria-targeted; R837.

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