Artesunate Nanoplatform Targets the Serine–MAPK Axis in Cancer‐Associated Fibroblasts to Reverse Photothermal Resistance in Triple‐Negative Breast Cancer
Abstract
Abstract Cancer‐associated fibroblasts (CAFs) play a pivotal role in inducing photothermal therapy (PTT) resistance of triple‐negative breast cancer (TNBC), but with unclear mechanism. Herein, aminoethyl anisamide‐modified nano‐biomimetic low‐density lipoprotein (A‐aLDL) is used to target deliver the PTT agent and artesunate (ARS) to both CAFs and cancer cells. Though CAFs are sensitive to PTT and notably transition to heat‐resistant phenotype, the formed protective barrier is destroyed by ARS. Subsequently, the outstanding anti‐tumor effects are achieved through PTT in multiple models with such kind of combination therapy. Interestingly, the mechanism is discovered that serine metabolism plays a major role in CAF resistance through spatially omics. ARS disrupts serine homeostasis, thereby attenuating the cascade activity of GTPases in MAPK pathway. Meanwhile, MAP2K7 is the most potential target for sensitizing PTT. By integrating ARS with PTT agents, the serine‐MAPK axis in CAFs is successfully modulated, thereby overcoming PTT resistance in TNBC therapy.
Article Details
Authors (20)
Dongdong Zheng
Jiaqi Yan
School of Engineering and Applied Sciences, Harvard University
Xuejiao Liu
Zhiming Zhang
State Key Laboratory of Vegetation Structure, Function and Construction (VegLab) and School of Ecology and Environmental Sciences, Yunnan University
Anqi Jin
Yue Zhao
Lu Bai
Beijing Key Laboratory of Solid-State Battery and Energy Storage Process, Key Laboratory of Green Process and Engineering, State Key Laboratory of Mesoscience and Process Engineering
Mengyao Quan
Department of Ultrasound Fudan University Shanghai Cancer Center Shanghai 200032 P. R. China
Xiuzhu Qi
Department of Ultrasound Fudan University Shanghai Cancer Center Shanghai 200032 P. R. China
Bin Fu
State Key Laboratory of Medical Proteomics
Zhigang Wu
Taizhou Research Institute
Jin Zhou
Department of Oncology Sichuan Cancer Hospital Chengdu China
Han Han
Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States
Ziqi Wang
Division of Advanced Materials
Shiyu Wang
Chaoqiang Deng
Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering Shanghai 200032 P. R. China
Weijian Sun
Cai Chang
Department of Ultrasound Fudan University Shanghai Cancer Center Shanghai 200032 P. R. China
Shichong Zhou
Hongbo Zhang