MITOCHONDRIA TARGETED DELIVERY OF SIMVASTATIN AND ITS CYTOTOXICITY TOWARD TRIPLE NEGATIVE BREAST CANCER (TNBC)

• Main Author: Valencia Cahyadinata, Elisse
• Format: Final Project
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/78450
• Institution: Institut Teknologi Bandung

Triple-negative breast cancer (TNBC) is a type of breast cancer that doesn’t express hormones and HER2 receptors. TNBC is linked with poor prognosis, increased metastasis, and recurrence rates. Current therapies that exist right now are limited and chemoresistance cases are common, therefore there needs to be an alternative strategy for TNBC therapy. Mitochondria is an essential organelle for the cell which is involved in energy synthesis and intrinsic apoptosis pathway. Delivery of mitotoxic compounds to mitochondria can cause mitochondrial dysfunction and makes the cell become non-viable. Simvastatin is a cholesterol-lowering drug from the statin group. There are previous reports that suggest simvastatin can cause mitochondrial dysfunction, therefore simvastatin can be used as a mitotoxic compound. In this research, a liposome-based mitochondria targeting drug delivery system of simvastatin incorporated with a mitochondriotropic compound, dequalinium chloride (DQA), is developed. Lipid components used are 1,2-dioleyl-sn-glycero-3- phosphoethanolamine (DOPE) and cholesterol. Liposome and Liposome-DQA (LipoDQ) were made using the thin film hydration method, followed by sonication. Nanoparticles with size <250, polydispersity index <0,3, and encapsulation efficiency >80% are obtained. Zeta potential measurement shows a shift from -22,46 in Liposome sample to +2,34 in LipoDQ sample, this shows the successful incorporation of DQA to the liposome’s system. Observation of nanoparticle accumulation using Confocal Laser Scanning Microscopy (CLSM) toward the 4T1 cell line shows that LipoDQ can be accumulated in the cell’s mitochondria. Cytotoxicity assay toward the 4T1 cell line shows that LipoDQ caused cytotoxicity at concentrations of 2,5 and 5 µM. There is no cytotoxicity observed on cells that are transfected with Liposome and LipoDQ blank. These results show mitochondria-targeted delivery of simvastatin can induce cell death.