Research Advances in Nanodrugs Targeting Lipid Metabolism Reprogramming for Colorectal Cancer Therapy.

Colorectal cancer (CRC) remains a major global health burden, with limited efficacy of conventional treatments due to tumor heterogeneity, drug resistance, and systemic toxicity. Lipid metabolism reprogramming has emerged as a hallmark of CRC progression, influencing tumor growth, metastasis, and therapy resistance. Concurrently, nanomedicine offers innovative platforms for targeted drug delivery to to inhibit tumor progression by intervening in the lipid metabolism, including modulation of lipid synthesis, uptake, storage, and cholesterol metabolism. This review provides an integrated perspective, systematically summarizing therapeutic strategies and research progress on nanodrugs targeting lipid metabolic reprogramming in CRC. We highlight nanoplatforms engineered to deliver inhibitors of key enzymes and signaling pathways, such as PI3K/AKT and Wnt/β-catenin. Representative nanoplatforms are discussed to illustrate diverse strategies for regulating lipid metabolic vulnerabilities in CRC, such as carrier-free nanoparticles, RBC membrane-coated nanocages and cholesterol-responsive nanoparticles. We also discuss the challenges in clinical translation, including tumor heterogeneity, biosafety, large-scale production, and clinical validation. Furthermore, we provide insight into translational challenges, emerging trends, and future directions for integrating lipid-targeted nanotherapies into clinical practice.