2. Academic Validation
  3. Hijacking the hyaluronan assisted iron endocytosis to promote the ferroptosis in anticancer photodynamic therapy

Hijacking the hyaluronan assisted iron endocytosis to promote the ferroptosis in anticancer photodynamic therapy

  • Carbohydr Polym. 2025 Mar 1:351:123123. doi: 10.1016/j.carbpol.2024.123123.
Hong Deng 1,  Jiayu Chen 2,  Huimin Wang 1,  Runmeng Liu 1,  Yiyi Zhang 1,  Hui Chang 3,  Ching-Hsuan Tung 4,  Weiqi Zhang 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Complex Severe and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, PR China.
  • 2 State Key Laboratory of Complex Severe and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, PR China; Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Xi'an 710069, PR China.
  • 3 Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Xi'an 710069, PR China.
  • 4 Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, NY 10065, USA.
  • 5 State Key Laboratory of Complex Severe and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, PR China. Electronic address: zwq@ibms.pumc.edu.cn.
PMID: 39779030 DOI: 10.1016/j.carbpol.2024.123123
Abstract

Photodynamic therapy (PDT) eradicates tumor cells by the light-stimulated Reactive Oxygen Species, which also induces lipid peroxidation (LPO) and subsequently Ferroptosis, an iron-depended cell death. Ferroptosis has a tremendous therapeutic potential in Cancer treatment, however, the Ferroptosis efficiency is largely limited by the available iron in cells. Through hijacking the CD44-mediated iron endocytosis of hyaluronan (HA), here PDT with enhanced Ferroptosis was realized by a HA@Ce6 nanogel self-assembled from HA, a photosensitizer Chlorin e6 (Ce6) and Fe3+ as cross-linkers. Taking advantages of HA's natural affinity towards CD44, HA@Ce6 enabled a targeted Ce6 delivery in CD44-overexpressed breast Cancer cells and meanwhile enhanced iron uptake to "fuel" Ferroptosis together with the light-stimulated LPO. Further, HA@Ce6 demonstrated an excellent Anticancer PDT efficacy and Ferroptosis induction in the murine 4 T1 xenograft model. This HA@Ce6 successfully exploited the role of HA in iron transport to sensitize Ferroptosis, providing a potent strategy to facilitate the Anticancer PDT.

Keywords

Chlorin e6; Ferroptosis; Hyaluronan; Nanogels; Photodynamic therapy; iron transport.

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