2. Academic Validation
  3. Genetically engineered GSDME vesicle coated nanoparticle for immune activating and pyroptosis inducing synergetic therapy of fibrosarcoma

Genetically engineered GSDME vesicle coated nanoparticle for immune activating and pyroptosis inducing synergetic therapy of fibrosarcoma

  • Mater Today Bio. 2025 Apr 26:32:101802. doi: 10.1016/j.mtbio.2025.101802.
Fenglin Miao 1 2 3 4,  Zhao Wang 1 3 4,  Qing Wang 3,  Changsheng Zhou 1 3 4 5,  Xiao Zhou 1 3 4,  Jialiang Zheng 1 3 4 6,  Yuan Ma 1 3 4,  Zhenhang Lin 1 3 4,  Yilai Gao 1 3 4,  Ting Wu 1 3 4,  Yong Zhang 7 8,  Jing Gao 9,  Wengang Li 1 3 4
Affiliations

Affiliations

  • 1 Cancer Research Center, School of Medicine, Xiamen University, Xiamen, 361102, China.
  • 2 Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250014, China.
  • 3 Xiamen University Research Center of Retroperitoneal Tumor Committee of Oncology Society of Chinese Medical Association, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361102, China.
  • 4 Shanghai Jiangxia Blood Science and Technology Company Joint Laboratory, School of Medicine, Xiamen University, Xiamen, 361102, China.
  • 5 Department of Hepatobiliary Surgery, Guizhou Provincial People's Hospital, Guiyang, 550002, China.
  • 6 Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, Zhejiang, China.
  • 7 Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200030, China.
  • 8 Department of Retroperitoneal Tumor and Soft Tissue Sarcoma Surgery, Fudan University, Shanghai, 200030, China.
  • 9 Department of Otorhinolaryngology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361102, China.
PMID: 40948580 DOI: 10.1016/j.mtbio.2025.101802
Abstract

Fibrosarcoma is a kind of highly malignant sarcoma with high recurrence rate after surgery and unsatisfying efficacy of radiotherapy and chemotherapy. Increasing the concentration of gasdermin in tumor cell to induce Pyroptosis is a promising strategy to treat fibrosarcoma. However, the poor cytotoxic T lymphocytes (CTL) infiltration in tumor area limits the therapeutic effect with disabled positive feedback between Pyroptosis and anti-tumor immunity. Induing tumor immunogenic cell death to activate anti-tumor immune and delivering gasdermin E (GSDME) to enhance tumor Pyroptosis will rebuild the positive feedback. Hence, we proposed and constructed a genetically engineered GSDME vesicle coated nanoparticle (HV-FI) to achieve effective treatment of fibrosarcoma. First, the GSDME membrane-expressing tumor cells are constructed and the GSDME-displaying vesicles are extracted. Then the HV-FI is prepared by hybridizing red blood cell membranes and encapsulating ICG-loaded mesoporous Fe3O4 nanoparticles. The GSDME proteins on the vesicles can effectively induce fibrosarcoma cell Pyroptosis with granzyme B. After NIR irradiation, fibrosarcoma cells released DAMPs and activated dendritic cells in vitro. In animal experiments, fibrosarcoma cells underwent Pyroptosis and CTL infiltration was boosted in tumor microenvironment. That subsequently enhanced tumor cell Pyroptosis with delivered GSDME, creating a synergetic effect of tumor cell Pyroptosis and anti-tumor immune activation, ultimately leading to effective tumor clearance. Meanwhile, the immunological memory is established, preventing tumor recurrence after treatment. This work proposes and validates the applicability and effectiveness of nanotherapy based on enhanced tumor Pyroptosis induction and immune activation, providing a new method for the treatment of unresectable fibrosarcoma.

Keywords

Genetically engineered vesicle; Immune activation; Pyroptosis induction; Synergy therapy; Targeted delivery of GSDME.

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