Dataset Information

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

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.

SUBMITTER: Dong Y

PROVIDER: S-EPMC11321661 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Dong Yunze Y Luo Jun J Pei Mingliang M Liu Shuai S Gao Yuchen Y Zhou Hongmin H Nueraihemaiti Yimingniyizi Y Zhan Xiangcheng X Xie Tiancheng T Yao Xudong X Guan Xin X Xu Yunfei Y

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20240617 30

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 path ...[more]

PMID: 38884220

Similar Datasets

Project description:BackgroundBoth oxidative stress and autoimmune responses play crucial roles in the development of vitiligo. Under oxidative stress, the apoptotic melanocytes expose self-antigens and release high mobility group box 1 (HMGB1), triggering autoimmune activation and recruiting CD8+ T cells. This process further leads to the destruction of melanocytes, resulting in the lack of melanin granules. Additionally, the accumulated CD8+ T cells release interferon-γ (IFN-γ) to activate janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in keratinocytes. Both oxidative stress and IFN-γ-JAK-STAT activation induce keratinocytes to express and release T cell chemotactic factors, exacerbating the process of vitiligo. Reducing the accumulation of CD8+ T cells by safeguarding melanocytes and keratinocytes from oxidative stress may be contemplated as a promising approach for vitiligo therapy.ResultsIn this study, we introduce a novel therapeutic agent called PDA-JAKi, which is capable of both eliminating oxidative stress and inhibiting T cell activation. Specifically, we have incorporated the janus kinase inhibitor (JAKi) tofacitinib into antioxidant polydopamine (PDA) nanoparticles, resulting in the formation of uniform PDA-JAKi nanodrug. PDA-JAKi effectively mitigates oxidative stress-induced apoptosis in melanocytes, reducing the antigen presentation and release of HMGB1. In addition, PDA-JAKi simultaneously attenuates oxidative stress and blocks the IFN-γ-JAK-STAT pathway to reduce the expression of C-X-C motif chemokine ligand 9/10/16 (CXCL9/10/16) in keratinocytes. We precisely deliver this therapeutic agent to the dermis using microneedle (MN) patches, aiming to enhance therapeutic efficacy compared to traditional drug administration methods. After PDA-JAKi MN treatment, the symptoms of vitiligo in mice are alleviated, and the affected areas regain pigmentation. Enhancements have been observed in the dermal thickness, the numbers of melanocytes and the content of melanin within the treated skin area. Moreover, there is a notable reduction in reactive oxygen species (ROS) level. Concurrently, substantial decreases were noted in CD8+ T cell infiltration, as well as the levels of IFN-γ and chemotactic factors CXCL9/10/16.ConclusionsIn summary, PDA-JAKi MN patches emerge as a promising therapeutic agent for vitiligo treatment.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets