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Targeting cancer-associated fibroblasts with hydroxyethyl starch nanomedicine boosts cancer therapy

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Abstract

Cancer-associated fibroblasts (CAFs) play an important role in facilitating the progression of triple-negative breast cancer (TNBC) by deteriorating the tumor mechanical microenvironment (TMME). Herein, we designed a CAFs-targeting nanomedicine by conjugating doxorubicin (DOX)-loaded hydroxyethyl starch-IR780 nanoparticles (NPs) with Cys-Arg-Glu-Lys-Ala (CREKA) peptide, which had a special affinity for fibronectin overexpressed on CAFs. After systemic administration, the NPs efficiently targeted CAFs and generated hyperthermia upon light irradiation, decreasing CAFs through the combination of chemo- and photothermal-therapies. Thus, a series of changes in TMME were achieved by reducing CAFs, which further disrupted the niche of cancer stem cells (CSCs) to affect their survival. As a result, the tumor growth was significantly inhibited in 4T1 tumors. The strategy of TMME modulation and CSCs elimination through targeting and depleting CAFs provides a novel therapeutic treatment for desmoplastic solid tumors.

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Acknowledgements

We thank the Research Core Facilities for Life Science (HUST), the Optical Bioimaging Core Facility of WNLO-HUST, and the Analytical and Testing Center of HUST for the facility support. This work was financially supported by grants from the National Research and Development Program of China (Nos. 2018YFA0208900, 2020YFA0211200, and 2020YFA0710700), the National Natural Science Foundation of China (Nos. 82172757 and 31972927), the Scientific Research Foundation of Huazhong University of Science and Technology (No. 3004170130), the Program for HUST Academic Frontier Youth Team (No. 2018QYTD01), and the HCP Program for HUST.

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Author notes

  1. Chong Wang, Huimin Wang, and Hai Yang contributed equally to this work.

Authors and Affiliations

  1. National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China

    Chong Wang, Huimin Wang, Hai Yang, Chen Xu, Qiang Wang, Zheng Li, Zhijie Zhang, Jiankun Guan, Xiangliang Yang & Zifu Li

  2. GBA Research Innovation Institute for Nanotechnology, Guangzhou, 510530, China

    Hai Yang & Xiangliang Yang

  3. Key Laboratory of Biomedical Photonics (HUST), Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430074, China

    Ximiao Yu & Xiaoquan Yang

  4. Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China

    Xiangliang Yang & Zifu Li

  5. Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medical, Huazhong University of Science and Technology, Wuhan, 430074, China

    Xiangliang Yang & Zifu Li

  6. Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, Huazhong University of Science and Technology, Wuhan, 430074, China

    Zifu Li

  7. Hubei Bioinformatics and Molecular Imaging Key Laboratory, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China

    Xiangliang Yang & Zifu Li

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  1. Chong Wang
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  2. Huimin Wang
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  3. Hai Yang
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  4. Chen Xu
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  5. Qiang Wang
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  8. Jiankun Guan
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  9. Ximiao Yu
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  10. Xiaoquan Yang
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  11. Xiangliang Yang
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  12. Zifu Li
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Correspondence to Zifu Li.

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Wang, C., Wang, H., Yang, H. et al. Targeting cancer-associated fibroblasts with hydroxyethyl starch nanomedicine boosts cancer therapy. Nano Res. 16, 7323–7336 (2023). https://doi.org/10.1007/s12274-023-5394-7

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  • DOI: https://doi.org/10.1007/s12274-023-5394-7

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