Rewiring cholesterol vulnerabilities with biomaterials: Mechanisms and opportunities for cancer therapy
- 1Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, China
- 2School of Dentistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA
Abstract
Tumor progression is accompanied by adaptive metabolic rewiring that extends beyond energy and amino acid metabolism to lipid networks. Among these alterations, disrupted cholesterol homeostasis has emerged as a key driver of tumor proliferation, migration, invasion, chemoresistance and immune escape. Cholesterol metabolism also shapes immune cell function, thereby linking tumor-intrinsic metabolic adaptation to immune remodeling in the tumor microenvironment. Recent advances in biomaterial-based therapeutics have expanded the scope of cholesterol-targeted cancer therapy. This Review summarizes how engineered biomaterials regulate cholesterol supply and uptake, intracellular cholesterol trafficking, membrane organization and cholesterol oxidation, and how these strategies reshape tumor cell survival, therapeutic resistance and antitumor immunity. We further discuss the integration of cholesterol-targeted biomaterials with chemotherapy, photodynamic therapy, sonodynamic therapy and immunotherapy, as well as key translational challenges, including metabolic compensation, preservation of cholesterol balance in normal tissues, the context-dependent biological effects of sterol products and the need for product-resolved analysis, since changes in total cholesterol or ROS alone cannot establish their identity or activity, and therapeutic heterogeneity across cholesterol-dependent tumor phenotypes. Biomaterials that target cholesterol metabolism offer a promising route to overcome therapy resistance and improve combination immunotherapy, but their clinical translation will require precise definition of responsive tumor types, target cell populations and actionable metabolic vulnerabilities.
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BibTeX
@article{chen2026rewiring,
title = {{Rewiring cholesterol vulnerabilities with biomaterials: Mechanisms and opportunities for cancer therapy}},
author = {Xu Chen and Meiyan Zou and Zili Chen and Jinhong Wu and Guiye Wu and Zihao Zhou and Rongwei Xu and Nina Li and Weiyao Feng and Zhiyu Guo and Xinyuan Zhao and Li Cui},
journal = {Materials Today Bio},
year = {2026},
month = oct,
doi = {10.1016/j.mtbio.2026.103762},
url = {https://doi.org/10.1016/j.mtbio.2026.103762},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Rewiring cholesterol vulnerabilities with biomaterials: Mechanisms and opportunities for cancer therapy
AU - Xu Chen
AU - Meiyan Zou
AU - Zili Chen
AU - Jinhong Wu
AU - Guiye Wu
AU - Zihao Zhou
AU - Rongwei Xu
AU - Nina Li
AU - Weiyao Feng
AU - Zhiyu Guo
AU - Xinyuan Zhao
AU - Li Cui
PY - 2026
DA - 2026/10/24
JO - Materials Today Bio
DO - 10.1016/j.mtbio.2026.103762
UR - https://doi.org/10.1016/j.mtbio.2026.103762
AB - Tumor progression is accompanied by adaptive metabolic rewiring that extends beyond energy and amino acid metabolism to lipid networks. Among these alterations, disrupted cholesterol homeostasis has emerged as a key driver of tumor proliferation, migration, invasion, chemoresistance and immune escape. Cholesterol metabolism also shapes immune cell function, thereby linking tumor-intrinsic metabolic adaptation to immune remodeling in the tumor microenvironment. Recent advances in biomaterial-based therapeutics have expanded the scope of cholesterol-targeted cancer therapy. This Review summarizes how engineered biomaterials regulate cholesterol supply and uptake, intracellular cholesterol trafficking, membrane organization and cholesterol oxidation, and how these strategies reshape tumor cell survival, therapeutic resistance and antitumor immunity. We further discuss the integration of cholesterol-targeted biomaterials with chemotherapy, photodynamic therapy, sonodynamic therapy and immunotherapy, as well as key translational challenges, including metabolic compensation, preservation of cholesterol balance in normal tissues, the context-dependent biological effects of sterol products and the need for product-resolved analysis, since changes in total cholesterol or ROS alone cannot establish their identity or activity, and therapeutic heterogeneity across cholesterol-dependent tumor phenotypes. Biomaterials that target cholesterol metabolism offer a promising route to overcome therapy resistance and improve combination immunotherapy, but their clinical translation will require precise definition of responsive tumor types, target cell populations and actionable metabolic vulnerabilities.
SN - 2590-0064
ER -