Integrated Cultivation and Empowerment for Healthy Aging | Professor Zhang Xianzheng of Wuhan University Publishes in Advanced Materials, Revealing a Novel Strategy for Reprogramming Aging (IF: 26.8)
Release Date:
2025-12-09 16:13
Recently, Professor Xianzheng Zhang, School of Chemistry and Molecular Sciences, Wuhan University Team In the top-tier materials science journal “ Advanced Materials published a research paper titled “Senescence Reprogramming Unleashes Tumor Immune Surveillance via Coordinated Gene Modulation.” This study proposes an innovative cancer treatment strategy that achieves tumor-specific senescence reprogramming by synergistically regulating two key targets—P16INK4a and PD-L1—thereby activating the immune system to combat tumors.
Paper Information
Title : Senescence Reprogramming Unleashes Tumor Immune Surveillance via Coordinated Gene Modulation
Chinese Title Aging reprogramming unleashes tumor immune surveillance through coordinated gene regulation.
Journal : Advanced Materials
Impact factor : 26.8
Author's Affiliation : School of Chemistry and Molecular Sciences, Wuhan University
Publication Date : December 1, 2025
Digital Object Identifier :doi/10.1002/adma.202516597
Research Background
Cellular senescence can recruit immune cells via the senescence-associated secretory phenotype (SASP) for cancer therapy; however, its efficacy is often constrained by immune tolerance and the immunosuppressive tumor microenvironment (TME).
Research Content
The team has engineered a uPAR-targeted gene-delivery nanosystem (TEPP) that specifically induces SASP-mediated immune activation in tumor cells while simultaneously blocking PD-L1–mediated immunosuppression, thereby converting immunologically “cold” tumors into “hot” tumors. In multiple preclinical models, TEPP monotherapy markedly inhibits tumor growth and metastasis; when combined with immune checkpoint inhibitors, its antitumor efficacy is further enhanced.
Research Innovations
Collaborative Regulation Mechanism: Achieve tumor-specific senescence reprogramming by simultaneously modulating P16INK4a and PD-L1.
Delivery System Innovation: A tumor-targeted gene-delivery nanoplatform, TEPP, has been developed to enhance therapeutic specificity and reduce systemic toxicity.
Immune Microenvironment Remodeling: It not only activates the immune response but also reverses immunosuppression, thereby enhancing the efficacy of immunotherapy through a dual-pronged approach.
Significance and Prospects of the Study
This study not only unveils novel mechanisms underlying the coordinated regulation of aging and immunity, but also provides a critical technological platform and theoretical foundation for the development of combined strategies that integrate tumor-targeted delivery systems with immunotherapy. The research demonstrates that this platform exhibits robust modularity and scalability, enabling future integration with oncolytic viruses, attenuated Salmonella, and other agents to enhance targeting efficiency. Moreover, it can be combined with adoptive cell therapies—such as CAR-T and CAR-NK—to further bolster the durability and potency of anti-tumor immune responses.
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