Multifunctional Nanomaterials Mediate Cholesterol Depletion for Cancer Treatment

• Published in: Angewandte Chemie Vol. 136; no. 46
• Main Authors: Zhen, Wenyao, Germanas, Tomas, Weichselbaum, Ralph R., Lin, Wenbin
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 11.11.2024
• Subjects: Cancer; Cancer therapies; Cellular stress response; Cholesterol; Immune checkpoint; immune checkpoints; Immune response; Immune system; Lipid metabolism; Metabolic pathways; Metabolites; Nanomaterials; Nanotechnology; Oxidative metabolism; Oxidative stress; Reviews; Tumor microenvironment; tumor therapy; Tumors
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202412844

Cholesterol is an essential membrane component, and the metabolites from cholesterol play important biological functions to intricately support cancer progression and dampen immune responses. Preclinical and clinical studies have demonstrated the role of cholesterol metabolism regulation on inhibiting tumor growth, remodeling the immunosuppressive tumor microenvironment (TME), and enhancing anti‐tumor immunity. In this minireview, we discuss complex cholesterol metabolism in tumors, its important role in cancer progression, and its influences on immune cells in the TME. We provide an overview of recent advances in cancer treatment through regulating cholesterol metabolism. We discuss the design of cholesterol‐altering multifunctional nanomaterials to regulate oxidative stress, modulate immune checkpoints, manipulate mechanical stress responses, and alter cholesterol metabolic pathways. Additionally, we examine the interactions between cholesterol metabolism regulation and established cancer treatments with the aim of identifying efficient strategies to disrupt cholesterol metabolism and synergistic combination therapies for effective cancer treatment. In this minireview, we briefly discuss multiple roles of cholesterol in cancer progression, tumor microenvironment, and immune responses. We then summarize recent advances in cancer treatment through regulating cholesterol metabolism using multifunctional nanomaterials, via oxidative stress regulation, immune checkpoint modulation, mechanical stress response manipulation, and cholesterol metabolic pathway alteration.