2. Academic Validation
  3. Epigenetic Remodeling Hydrogel Patches for Multidrug-Resistant Triple-Negative Breast Cancer

Epigenetic Remodeling Hydrogel Patches for Multidrug-Resistant Triple-Negative Breast Cancer

  • Adv Mater. 2021 May;33(18):e2100949. doi: 10.1002/adma.202100949.
Xiaoyuan Ji 1,  Daoxia Guo 1,  Jia Ma 2,  Min Yin 3,  Yun Yu 4,  Chang Liu 4,  Yanfeng Zhou 1,  Jinli Sun 1,  Qian Li 5,  Nan Chen 3,  Chunhai Fan 5,  Haiyun Song 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • 2 School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China.
  • 3 College of Chemistry and Materials Science, Shanghai Normal University, Shanghai, 200234, China.
  • 4 Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • 5 School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
PMID: 33792093 DOI: 10.1002/adma.202100949
Abstract

The induced expansion of tumor-initiating cells (T-ICs) upon repeated exposure of tumors to chemotherapeutic drugs forms a major cause for chemoresistance and Cancer metastasis. Here, a tumor-microenvironment-responsive hydrogel patch is designed to modulate the plasticity of T-ICs in triple-negative breast Cancer (TNBC), which is insensitive to hormone- and HER2-targeting. The on-site formation of the hydrogel network patches tumors in a chemoresistant TNBC murine model and senses intratumoral Reactive Oxygen Species for linker cleavage and payload release. Patch-mediated inhibition of the Histone Demethylase lysine-specific demethylase 1 (LSD1) epigenetically regulates the switch of T-ICs from self-renewal to differentiation, rehabilitating their chemosensitivity. Moreover, the hydrogel patch enhances tumor immunogenicity and increases T-cell infiltration via epigenetic activation of innate immunity. A single-dose of the hydrogel patch harboring LSD1 inhibitor and chemotherapy agent efficiently suppresses tumor growth, postsurgical relapse, and metastasis. The superior efficacy against multidrug resistance further reveals the broad applicability of epigenetic remodeling hydrogel patches.

Keywords

epigenetic remodeling hydrogel patches; innate immunity; multidrug resistance; tumor-initiating cells.

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