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.
| Original language | English |
|---|---|
| Article number | 2502617 |
| Journal | Advanced Materials |
| Volume | 37 |
| Issue number | 35 |
| DOIs | |
| Publication status | Published - 4 Sept 2025 |
| MoE publication type | A1 Journal article-refereed |
Funding
The authors are grateful to Xiaochun Wan M.D. (Fudan University Shanghai Cancer center) for her evaluation recommendations on all tissue sections, Qian Zhou Ph.D., Siyi Cao Ph.D. and Fan Yang Ph.D. (Fudan University Shanghai Cancer center), Zhiguo Zhou Professor (Shanghai Normal University) for critically reading the manuscript. The authors also thank to Lian Li, Xiaohua Yao (Shanghai OEbiotech Co., Ltd. (Shanghai, China)) and Zhenyu Xu (Shanghai Lu Ming Biotech Co., Ltd. (Shanghai, China)) for their assistance in spatial omics and sc‐RNA seq analysis. 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.))
Keywords
- artesunate nanoplatform
- breast cancer
- cancer-associated fibroblasts
- photothermal therapy
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Åbo Akademi Functional Printing Center
Toivakka, M. (PI), Rosenholm, J. (PI), Anttu, N. (PI), Bobacka, J. (PI), Huynh, T. P. (PI), Peltonen, J. (PI), Wang, X. (PI), Wilen, C.-E. (PI), Xu, C. (PI), Zhang, H. (PI) & Österbacka, R. (PI)
Faculty of Science and EngineeringFacility/equipment: Facility
Projects
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MADNESS: Centre of Excellence in Materials-driven solutions for combatting antimicrobial resistance
Rosenholm, J. (Principal Investigator), Porres Paltor, I. (Co-Principal Investigator), Bansal, K. (Coordinator), Lafond, S. (Co-Principal Investigator), Uppstu, P. (Co-Principal Investigator), Viitala, T. (Co-Principal Investigator), Wang, X. (Co-Principal Investigator), Wilen, C.-E. (Co-Principal Investigator), Xu, C. (Co-Principal Investigator), Zhang, H. (Co-Principal Investigator), Lu, Z. (Co-Investigator), Verma, J. (Co-Investigator), Kumar, V. (Co-Investigator), Frejborg, F. (Co-Investigator), Wang, S. (Co-Investigator), Ran, M. (Co-Investigator), Ma, X. (Co-Investigator), Yang, W. (Co-Investigator), Liang, S. (Co-Investigator), Zhang, Y. (Co-Investigator), Fan, L. (Co-Investigator), Chen, Y. (Co-Investigator), Wang, L. (Co-Investigator), Zhuang, P. (Co-Investigator), Rajan Prakash, D. (Co-Investigator), Howaili, F. (Co-Investigator), Gulshan, R. (Co-Investigator), Yadav, D. (Co-Investigator), Pathak, C. (Co-Investigator), Mustafa, R. (Co-Investigator), Rostami, L. (Co-Investigator), Jafari Dargahlou, M. (Co-Investigator), Nygård, A. (Co-Investigator) & Manasut, P. (Co-Investigator)
01/01/24 → 31/12/28
Project: Foundation
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