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
来源：
Nano Research | 2023年 / 16卷 / 5期
关键词：
hydroxyethyl starch; cancer-associated fibroblasts; tumor mechanical microenvironment; cancer stem cells; combination therapy;
D O I：
暂无
中图分类号：
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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