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.
Abbreviations
27-HC, 27-hydroxycholesterol; ACAT-1, acyl-CoA cholesterol acyltransferase-1; ATP, adenosine triphosphate; CE, cholesterol esters; COD, cholesterol oxidase; DLBCL, diffuse large B-cell lymphoma; DOX, doxorubicin; DOX@MOF-COD@CS, DOX loaded nanosystem with a cholesterol cascade catalytic consumption; EALP, matrix metalloproteinase-2 -sensitive tumor-penetrable nanovesicle; EMT, epithelial-mesenchymal transition; FDPS, farnesyl diphosphate synthase; HA, hyaluronic acid; HACE, hyaluronic acid-ceramide; HACE-MbCD NA, hyaluronic acid-ceramide- methyl-β-cyclodextrin nanoassembly; HDL, high-density lipoprotein; HDL NPs, high-density lipoprotein nanoparticles; HMGCR, hydroxy-3-methylglutaryl-CoA reductase; ICIs, immune checkpoint inhibitors; LR, lipid raft; LXR, liver X receptor; MDR, multidrug resistance; MOF, metal–organic framework; mTORC1, mammalian target of rapamycin C1; MβCD/MbCD, methyl-β-cyclodextrin; NPC1, niemann-pick C1 protein; p-gp, p-glycoprotein; PTX, paclitaxel; SCARB1, scavenger receptor type B1; Smo, smoothened; SREBP2, sterol regulatory element-binding protein 2; STARD3, steroidogenic acute regulatory related lipid transfer domain-3; SV, simvastatin; TAMs, tumor-associated macrophages; TME, tumor microenvironment; WGA-TA-sHDL, withalongolide A 4,19,27-triacetate loaded synthetic HDL nanodisks.
Disclosure
The authors report no conflicts of interest in this work.