Mammary organoid-based depot for post-surgical chemotherapy and gland regeneration

  • Nat Biomed Eng. 2026 Apr 17. doi: 10.1038/s41551-026-01655-1.
Shenqiang Wang  #  1  2 ,  Yinxian Yang  #  3 ,  Yanfang Wang  3 ,  Jinpeng Han  3 ,  Tong Hu  4 ,  Sheng Zhao  3 ,  Feng Liu  3 ,  Xinmin Yu  3 ,  Tingxizi Liang  3 ,  Yuqi Zhang  3  5 ,  Huili Hu  6 ,  Jicheng Yu  7  8  9  10 ,  Zhen Gu  11  12  13  14  15  16
Affiliations
  • 1. State Key Laboratory of Advanced Drug Delivery and Release Systems, School of Pharmacy, Zhejiang University, Hangzhou, China. [email protected].
  • 2. Engineering Research Center of RNA Medicine and Cell Therapy Technology, Ministry of Education, College of Pharmaceutical Sciences, Soochow University, Suzhou, China. [email protected].
  • 3. State Key Laboratory of Advanced Drug Delivery and Release Systems, School of Pharmacy, Zhejiang University, Hangzhou, China.
  • 4. Engineering Research Center of RNA Medicine and Cell Therapy Technology, Ministry of Education, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
  • 5. Department of Burns and Wound Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
  • 6. The Key Laboratory of Experimental Teratology, Ministry of Education, Department of Systems Biomedicine, School of Basic Medical Sciences, Shandong University, Jinan, China. [email protected].
  • 7. State Key Laboratory of Advanced Drug Delivery and Release Systems, School of Pharmacy, Zhejiang University, Hangzhou, China. [email protected].
  • 8. Jinhua Institute of Zhejiang University, Jinhua, China. [email protected].
  • 9. Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. [email protected].
  • 10. Zhejiang Key Laboratory of New Drug Intelligent Innovation for Metabolic Diseases, Zhejiang University, Hangzhou, China. [email protected].
  • 11. State Key Laboratory of Advanced Drug Delivery and Release Systems, School of Pharmacy, Zhejiang University, Hangzhou, China. [email protected].
  • 12. Jinhua Institute of Zhejiang University, Jinhua, China. [email protected].
  • 13. Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. [email protected].
  • 14. Liangzhu Laboratory, Zhejiang University, Hangzhou, China. [email protected].
  • 15. MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, China. [email protected].
  • 16. Institute of Fundamental and Transdisciplinary Research Zhejiang University, Zhejiang University, Hangzhou, China. [email protected].
  • # Contributed equally.
PMID: 41998163 DOI: 10.1038/s41551-026-01655-1
Abstract

Preventing Cancer recurrence after surgical removal, while preserving breast cosmesis and restoring function, remains challenging. Traditional scaffold-based approaches are often restricted by their inadequate integration with natural tissues and unmatched rate of material degradation to tissue development. Here we report an Anticancer drug secretion system based on engineered mammary organoids for inhibiting post-surgical tumour recurrence and promoting tissue reconstruction. By inducing the lactation of mammary organoids, cytoplasmic lipid droplets form intracellularly. A pH-responsive prodrug, comprising all-trans retinal and the chemotherapeutic agent doxorubicin, is readily encapsulated in these lipid droplets. Upon lactation, milk fat globules, enriched with these drug-loaded lipid droplets, are released to residual tumour cells through the contractile actions of myoepithelial cells. Both mouse and human-induced pluripotent stem cell-derived mammary organoids were engineered as drug-secreting depots and demonstrated their effectiveness in inhibiting tumour recurrence (96% regression) in a mouse post-surgical Breast Cancer model. In addition, the organoids could be self-adaptively integrated with mammary glands and contribute to their reconstruction, ultimately restoring lactational capacity in the recipient mice.

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