DataVXAdvanced Functional MaterialsPaper
journal article·2026-04Open access

A One‐Two Punch Strategy Against Cancer: Simultaneously Inducing and Eliminating Senescent Tumor Cells

Bo Fang, Fei Pan, Sailing Chen, Wenli Tian, Yang Zhu, Yaobang Shen, Hao Wang, Hui Guo, Yuan Ding, Yuhao Wang, Gaopeng Li, Daqian Xu, Zhongquan Sun, Xiao Li, Zhengwei Mao

Advanced Functional Materials· Volume 36· Issue 27
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Source abstract

Abstract

Abstract Senolytics, an emerging class of agents that selectively deplete pro‐tumorigenic senescent cells, offer a novel adjuvant strategy to re‐engineer the tumor microenvironment and potentiate anticancer therapy. However, direct senolytic treatment poses significant safety risks, and selectively eliminating senescent cells to treat tumors remains a substantial challenge. Here, a metal‐polyphenol network (MPN) therapeutic platform operates through a “one‐two punch” strategy. The platform exploits metal‐polyphenol coordination to co‐assemble Fe 3 ⁺, folate‐terminated polyethylene glycol (PEG), a disulfide‐bridged dasatinib prodrug, and quercetin into stable nanoparticles (DQ NPs). Folate–PEG confers active tumor targeting on DQ NPs while locally released Fe 3 + pushes tumor cells into senescence, and the high intratumoral glutathione (GSH) level together with the acidic microenvironment activate the prodrug to enable dasatinib and quercetin to synergistically clear the senescent cells. Owing to their dual pH‐ and GSH‐responsiveness, these DQ NPs specifically induce senescence and then eradicate senescent tumor cells, resulting in potent tumor growth suppression. Both in vitro and in vivo studies reveal markedly superior antitumor efficacy over conventional senolytics. Comprehensive toxicological analyses further demonstrate tumor‐selective accumulation and an excellent safety profile. Collectively, our work presents a dual‐responsive MPN platform that integrates senescence induction with selective clearance, offering a new paradigm for cancer therapy.
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Research context

Nanomaterials

OpenAlex topics: Telomeres, Telomerase, and Senescence · Click Chemistry and Applications · Nanoplatforms for cancer theranostics

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated Hospital Zhejiang University School of Medicine Zhejiang University Hangzhou 310009 China

State Key Laboratory of Resource Insects Institute of Apicultural Research Chinese Academy of Agricultural Sciences Beijing 100093 China

Department of Gynecologic Oncology Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital Zhejiang University School of Medicine Hangzhou 310006 China

MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and Engineering Zhejiang University Hangzhou 310058 China

CAS Center for Excellence in Nanoscience CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety National Center for Nanoscience and Technology Beijing 100190 China

State Key Laboratory of Quality Research in Chinese Medicine School of Pharmacy Macau University of Science and Technology Macao 999078 China

Zhejiang Provincial Key Laboratory of Pancreatic Disease The First Affiliated Hospital Institute of Translational Medicine Zhejiang University School of Medicine Zhejiang University Hangzhou 310029 China

Institute of Fundamental and Transdisciplinary Research Cancer Center Zhejiang University Hangzhou 310058 China

Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism Zhejiang University Hangzhou 310029 China

Department of Colorectal Surgery and Oncology The Second Affiliated Hospital and Institute of Translational Medicine Zhejiang University School of Medicine Zhejiang University Hangzhou 310009 China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China

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