2. Academic Validation
  3. Prodrug nanoplatform for triggering ferroptosis to eliminate senescent cells in age-associated pathologies

Prodrug nanoplatform for triggering ferroptosis to eliminate senescent cells in age-associated pathologies

  • Nat Commun. 2025 Dec 13. doi: 10.1038/s41467-025-67364-6.
Chengkang Jin # 1 2,  Xiaoling Xu # 3 4,  Ning Yao 5,  Hairui Zhang 6,  Changjiang Chen 7,  Lingyao Zeng 1 8,  Zhiyun Liu 1 8,  Lanjie Lei 1,  Shumao Cui 9,  Chengping Wen 10,  Liyun Shi 11
Affiliations

Affiliations

  • 1 Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, Zhejiang, China.
  • 2 College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China.
  • 3 Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, Zhejiang, China. [email protected].
  • 4 Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China. [email protected].
  • 5 Department of General Surgery, Joint Support Force 903th Hospital, Hangzhou, China.
  • 6 School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
  • 7 Department of Immunology and Medical Microbiology, Nanjing University of Chinese Medicine, Nanjing, China.
  • 8 Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China.
  • 9 State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, China.
  • 10 College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China. [email protected].
  • 11 Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, Zhejiang, China. [email protected].
  • # Contributed equally.
PMID: 41390693 DOI: 10.1038/s41467-025-67364-6
Abstract

Accumulation of senescent cells is associated with aging and age-related diseases. However, current clearance therapies targeting senescent cells are often limited by low efficiency, poor specificity, and insufficient penetration. Here we develop a nano-platform composed of a probe (GD) that can be specifically activated by senescent cells, a Photosensitizer (Ce6), and a peptide (HK) for targeting ferritin, named HK-PCGC. We show that upon entering senescent cells, GD is activated by high levels of β-galactosidase, releasing fluorescence to excite Ce6. Ce6 then generates Reactive Oxygen Species to eliminate these cells. Additionally, we find that under the guidance of the peptide HK, our system degrades ferritin to trigger Ferroptosis, further eliminating senescent cells. Collectively, we demonstrate that HK-PCGC can effectively eliminate senescent cells, reduce the senescence-associated secretory phenotype, and safely improve the physical fitness of aged mice. This study integrates senescent cell responsiveness, laser-free photodynamic therapy, and induction of Ferroptosis, offering a potential approach for delaying aging.

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