Regulating Cholesterol in Tumorigenesis: A Novel Paradigm for Tumor Nanotherapeutics

Int J Nanomedicine. 2024 Feb 1:19:1055-1076. doi: 10.2147/IJN.S439828. eCollection 2024.

Abstract

During the past decade, "membrane lipid therapy", which involves the regulation of the structure and function of tumor cell plasma membranes, has emerged as a new strategy for cancer treatment. Cholesterol is an important component of the tumor plasma membrane and serves an essential role in tumor initiation and progression. This review elucidates the role of cholesterol in tumorigenesis (including tumor cell proliferation, invasion/metastasis, drug resistance, and immunosuppressive microenvironment) and elaborates on the potential therapeutic targets for tumor treatment by regulating cholesterol. More meaningfully, this review provides an overview of cholesterol-integrated membrane lipid nanotherapeutics for cancer therapy through cholesterol regulation. These strategies include cholesterol biosynthesis interference, cholesterol uptake disruption, cholesterol metabolism regulation, cholesterol depletion, and cholesterol-based combination treatments. In summary, this review demonstrates the tumor nanotherapeutics based on cholesterol regulation, which will provide a reference for the further development of "membrane lipid therapy" for tumors.

Keywords: cholesterol; nanotherapeutics; plasma membrane; tumor.

Publication types

  • Review

MeSH terms

  • Carcinogenesis
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Cholesterol / metabolism
  • Humans
  • Neoplasms* / drug therapy
  • Tumor Microenvironment

Substances

  • Cholesterol

Grants and funding

This study was financially supported by the National Natural Science Foundation of China (82103505 and 82071616), the Zhejiang Provincial Natural Science Foundation Public Welfare Projects of China (LTGC23H050001), and the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (2021RC005).