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Advanced Science

Advanced Science

IF: 14.3
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Biomimetic Hydrogel-Mediated Mechano-Immunometabolic Therapy for Inhibition of ccRCC Recurrence After Surgery.

Published:17 June 2024 DOI: 10.1002/advs.202308734 PMID: 38884220
Yunze Dong, Jun Luo, Mingliang Pei, Shuai Liu, Yuchen Gao, Hongmin Zhou, Yimingniyizi Nueraihemaiti, Xiangcheng Zhan, Tiancheng Xie, Xudong Yao, Xin Guan, Yunfei Xu

Abstract

The unique physical tumor microenvironment (TME) and aberrant immune metabolic status are two obstacles that must be overcome in cancer immunotherapy to improve clinical outcomes. Here, an in situ mechano-immunometabolic therapy involving the injection of a biomimetic hydrogel is presented with sequential release of the anti-fibrotic agent pirfenidone, which softens the stiff extracellular matrix, and small interfering RNA IDO1, which disrupts kynurenine-mediated immunosuppressive metabolic pathways, together with the multi-kinase inhibitor sorafenib, which induces immunogenic cell death. This combination synergistically augmented tumor immunogenicity and induced anti-tumor immunity. In mouse models of clear cell renal cell carcinoma, a single-dose peritumoral injection of a biomimetic hydrogel facilitated the perioperative TME toward a more immunostimulatory landscape, which prevented tumor relapse post-surgery and prolonged mouse survival. Additionally, the systemic anti-tumor surveillance effect induced by local treatment decreased lung metastasis by inhibiting epithelial-mesenchymal transition conversion. The versatile localized mechano-immunometabolic therapy can serve as a universal strategy for conferring efficient tumoricidal immunity in “cold” tumor postoperative interventions.

Substances (8)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Sorafenib 284461-73-0 C21H16ClF3N4O3 658 suppliers $8.00-$1529.00
Sorafenib 284461-73-0 C21H16ClF3N4O3 658 suppliers $8.00-$1529.00
Sorafenib 284461-73-0 C21H16ClF3N4O3 658 suppliers $8.00-$1529.00
Sorafenib 284461-73-0 C21H16ClF3N4O3 658 suppliers $8.00-$1529.00
Sorafenib 284461-73-0 - Inquiry
Sorafenib 284461-73-0 - Inquiry
2-?Pyridinecarboxamide, 4-?[4-?[[[[4-?chloro-?3-?(trifluoromethyl)?phenyl]?amino]?carbonyl]?amino]?phenoxy]?-?N-?methyl- 284461-73-0 - Inquiry
2-?Pyridinecarboxamide, 4-?[4-?[[[[4-?chloro-?3-?(trifluoromethyl)?phenyl]?amino]?carbonyl]?amino]?phenoxy]?-?N-?methyl- 284461-73-0 - Inquiry

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