纳米医学
癌症研究
肿瘤微环境
间质细胞
化学
转移
内化
医学
癌症
受体
材料科学
内科学
纳米技术
生物化学
肿瘤细胞
纳米颗粒
作者
Yuxin Zhang,Jie Zhou,Marc E. Rothenberg,Zhiqian Li,Ling Gu,Dayi Pan,Xiuli Zheng,Qian‐Feng Zhang,Rongjun Chen,Hu Zhang,Qiyong Gong,Zhongwei Gu,Kui Luo
标识
DOI:10.1016/j.jconrel.2023.03.015
摘要
Interaction between carcinoma-associated fibroblasts (CAFs) and tumor cells leads to the invasion and metastasis of breast cancer. Herein, we prepared a redox-responsive chondroitin sulfate (CS)-based nanomedicine, in which hydrophobic cabazitaxel (CTX) was conjugated to the backbone of CS via glutathione (GSH)-sensitive dithiomaleimide (DTM) to form an amphipathic CS-DTM-CTX (CDC) conjugate, and dasatinib (DAS) co-assembled with the CDC conjugate to obtain [email protected]. After CD44 receptor-mediated internalization by CAFs, the nanomedicine could reverse CAFs to normal fibroblasts, blocking their crosstalk with tumor cells and reducing synthesis of major tumor extracellular matrix proteins, including collagen and fibronectin. Meanwhile, the nanomedicine internalized by tumor cells could effectively inhibit tumor proliferation and metastasis, leading to shrinkage of the tumor volume and inhibition of lung metastasis in a subcutaneous 4T1 tumor model with low side effects. Collectively, the nanomedicine showed a remarkably synergistic therapy effect against breast cancer by modulating tumor-stromal crosstalk.
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