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

被引:0
作者
Chong Wang
Huimin Wang
Hai Yang
Chen Xu
Qiang Wang
Zheng Li
Zhijie Zhang
Jiankun Guan
Ximiao Yu
Xiaoquan Yang
Xiangliang Yang
Zifu Li
机构
[1] Huazhong University of Science and Technology,National Engineering Research Center for Nanomedicine, College of Life Science and Technology
[2] GBA Research Innovation Institute for Nanotechnology,Key Laboratory of Biomedical Photonics (HUST), Ministry of Education
[3] Huazhong University of Science and Technology,Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology
[4] Huazhong University of Science and Technology,Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medical
[5] Huazhong University of Science and Technology,Hubei Engineering Research Center for Biomaterials and Medical Protective Materials
[6] Huazhong University of Science and Technology,Hubei Bioinformatics and Molecular Imaging Key Laboratory, College of Life Science and Technology
[7] Huazhong University of Science and Technology,undefined
关键词
hydroxyethyl starch; cancer-associated fibroblasts; tumor mechanical microenvironment; cancer stem cells; combination therapy;
D O I
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学科分类号
摘要
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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页码:7323 / 7336
页数:13
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