title: Efficacy of edelfosine lipid nanoparticles in breast cancer cells.
abstract: Breast cancer is a heterogeneous group of neoplasms predominantly originating in the terminal duct lobular units. It represents the leading cause of cancer death in women and the survival frequencies for patients at advanced stages of the disease remain low. New treatment options need to be researched to improve these rates. The anti-tumor ether lipid edelfosine (ET) is the prototype of a novel generation of promising anticancer drugs. However, it presents several drawbacks for its use in cancer therapy, including gastrointestinal and hemolytic toxicity and low oral bioavailability. To overcome these obstacles, ET was encapsulated in Precirol ATO 5 lipid nanoparticles (ET-LN), and its anti-tumor potential was in vitro tested in breast cancer. The formulated ET-LN were more effective in inhibiting cell proliferation and notably decreased cell viability, showing that the cytotoxic effect of ET was considerably enhanced when ET was encapsulated. In addition, ET and ET-LN were able to promote cell cycle arrest at G1 phase. Moreover, although both treatments provoked an apoptotic effect in a time-dependent manner, such anti-tumor effects were noticeably improved with ET-LN treatment. Therefore, our results indicate that encapsulating ET in LN played an essential role in improving the efficacy of the drug.
authors: Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, C/ Irunlarrea no. 1, 31008 Pamplona, Spain.
authors: María Ángela
authors: MÁ
authors: Aznar
authors: Beatriz
authors: B
authors: Lasa-Saracíbar
authors: Ander
authors: A
authors: Estella-Hermoso de Mendoza
authors: María José
authors: MJ
authors: Blanco-Prieto
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004075:Diglycerides / Q000737:chemistry; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010742:Phospholipid Ethers / Q000008:administration & dosage* / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004075:Diglycerides; D010742:Phospholipid Ethers; D011136:Polysorbates; C026659:edelfosine; C009032:precirol
keywords: ALPs; Alkylphospholipids; B-LN; Breast cancer; EPR effect; ET; ET-LN; Edelfosine; IC(50); LN; Lipid nanoparticles; MCF7; MCL; PDI; PI; alkylphospholipids; blank (unloaded) nanoparticles; edelfosine; edelfosine-loaded lipid nanoparticles; enhanced permeability and retention effect; inhibitory concentration 50; lipid nanoparticles; mantle cell lymphoma; polydispersity index; propidium iodide