ArticleBioactive materials2024
Enhanced pyroptosis induction with pore-forming gene delivery for osteosarcoma microenvironment reshaping.
Article in Bioactive materials, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Disrupting membranes, controlling cell fate: the role of pore-forming proteins in cell death and therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- High-dose ascorbic acid selectively induces pyroptosis in LKB1-deficient lung cancer and sensitizes immunotherapy.Cell reports. Medicine · 2025Article
- Material-Driven Therapeutics: Functional Nanomaterial Design Paradigms Revolutionizing Osteosarcoma Treatment.Journal of functional biomaterials · 2025Review
- Harnessing multi‑omics to revolutionize understanding and management of osteosarcoma: A pathway to precision medicine (Review).International journal of molecular medicine · 2025Review
- Functional Materials Targeted Regulation of Gasdermins: From Fundamentals to Functionalities and Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
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Authors and funding
18 authors.
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Abstract
Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival. Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment (TME). Pore-forming gasdermins (GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME, however, the expressions and relationships of GSDMs with osteosarcoma remain unclear. Herein, gasdermin E (GSDME) expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients, and low GSDME expression was observed. A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction. Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction. The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction. The pyroptosis further initiated proinflammatory cytokines release, increased immune cell infiltration, activated adaptive immune responses and create a favorable immunogenic hot TME. The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma, but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma.
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