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Enzyme-Dynamic Extracellular Vesicles for Metalloimmunotherapy of Malignant Pleural Effusions.
- Source :
-
ACS nano [ACS Nano] 2024 Aug 20; Vol. 18 (33), pp. 21855-21872. Date of Electronic Publication: 2024 Aug 07. - Publication Year :
- 2024
-
Abstract
- Malignant pleural effusions (MPEs) are hard to treat, and their onset usually signals terminal cancer. Immunotherapies hold promise but must overcome the immunosuppressive MPE microenvironment. Herein, we treat MPEs via synergistically combining two emerging cancer therapy modalities: enzyme-dynamic therapy (EDT) and metalloimmunotherapy. To do so, a nanoplatform termed "A-R-SOME" was developed which comprises MPE-targeted M1 type extracellular vesicles (EVs) loaded with (1) a manganese-based superoxide dismutase (SOD) enzyme, (2) stimulator of interferon genes (STING) agonist diABZI-2, and (3) signal transducer and an activator of transcription 3 (STAT3) small interfering RNA. Endogenous reactive oxygen species within tumors induced immunogenic cell death by EDT, along with STING activation by both Mn and diABZI-2, and suppression of the STAT3 pathway. Systemically administered A-R-SOME alleviated the MPE immunosuppressive microenvironment, triggered antitumor systemic immunity, and long-term immune memory, leading to the complete eradication of MPE and pleural tumors with 100% survival rate in an aggressive murine model. A-R-SOME-induced immune effects were also observed in human patient-derived MPE, pointing toward the translation potential of A-R-SOME as an experimental malignancy treatment.
- Subjects :
- Animals
Humans
Mice
Superoxide Dismutase metabolism
Tumor Microenvironment drug effects
Antineoplastic Agents pharmacology
Antineoplastic Agents chemistry
RNA, Small Interfering genetics
Female
STAT3 Transcription Factor metabolism
Mice, Inbred C57BL
Reactive Oxygen Species metabolism
Cell Line, Tumor
Extracellular Vesicles chemistry
Extracellular Vesicles metabolism
Pleural Effusion, Malignant
Immunotherapy
Subjects
Details
- Language :
- English
- ISSN :
- 1936-086X
- Volume :
- 18
- Issue :
- 33
- Database :
- MEDLINE
- Journal :
- ACS nano
- Publication Type :
- Academic Journal
- Accession number :
- 39109520
- Full Text :
- https://doi.org/10.1021/acsnano.3c12375