Artesunate Nanoplatform Targets the Serine–MAPK Axis in Cancer‐Associated Fibroblasts to Reverse Photothermal Resistance in Triple‐Negative Breast Cancer - UTU Research Portal

A1 Refereed original research article in a scientific journal

Artesunate Nanoplatform Targets the Serine–MAPK Axis in Cancer‐Associated Fibroblasts to Reverse Photothermal Resistance in Triple‐Negative Breast Cancer

Authors: Zheng, Dongdong; Yan, Jiaqi; Liu, Xuejiao; Zhang, Zhiming; Jin, Anqi; Zhao, Yue; Bai, Lu; Quan, Mengyao; Qi, Xiuzhu; Fu, Bin; Wu, Zhigang; Zhou, Jin; Han, Han; Wang, Ziqi; Wang, Shiyu; Deng, Chaoqiang; Sun, Weijian; Chang, Cai; Zhou, Shichong; Zhang, Hongbo

Publisher: Wiley

Publishing place: WEINHEIM

Publication year: 2025

Journal: Advanced Materials

Journal name in source: Advanced Materials

Journal acronym: ADV MATER

Article number: 2502617

Volume: 37

Number of pages: 22

ISSN: 0935-9648

eISSN: 1521-4095

DOI: https://doi.org/10.1002/adma.202502617

Web address : https://doi.org/10.1002/adma.202502617

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/499520637

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.

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Advanced Materials - 2025 - Zheng - Artesunate Nanoplatform Targets the Serine MAPK Axis in Cancer‐Associated Fibroblasts.pdf

Funding information in the publication:
This study was supported by the National Science Foundation (Grant No. 82372145 (H.Z.)), the Joint Fund of the Zhejiang Provincial Natural Science Foundation of China (Grant No. BD24H180004 (H.Z.)), and the grant from the Discipline Cluster of Oncology, Wenzhou Medical University, China (Grant No. z1-2023002 (H.Z.)). It was also supported by the Research Project (Grant No. 347897 (H.Z.)), Solution for Health Profile (Grant No. 336355 (H.Z.)), InFLAMES Flagship (Grant No. 337531 (H.Z.)) and Printed Intelligence Infrastructure (PII-FIRI) from Research Council of Finland. The National Natural Science Foundation of China (Grant No. 82071945, 82371978, 82311530049 (S.Z.)), Shanghai Committee of Science and Technology, China (Grant No. 21S31905400 (S.Z.)), the National Natural Science Foundation of China (Grant No. 81830058 (C.C.)), and the Shanghai Anticancer Association EYAS PROJECT (Grant No. SACA-CY22C07 (D.Z.)), China Postdoctoral Science Foundation (Grant No. 2024M760561 (D.Z.))

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