Antiproliferative activity against Jurkat cells of SAHM1 peptide conjugated gold nanoparticles

Abstract

In general, treatments of cancer may involve medication, surgery, radiation and chemotherapy. Although these treatments are successful at a certain satisfactory level, their side effects are not acceptable for some patients. Thus, many researches have been investigated alternative methods to cure cancer. A technique of interest is the use of targeted drug therapy in which drug is designed to selectively kill only the cancer cells and to do no harm on the normal cells. Stapled α-helical peptide derived from mastermind-like I or SAHM1 is a small peptide which has been reported to have antiproliferative activity against cancer cells. However, its use is limited by degradation during cell penetration and transport inside the cell. In this study, gold nanoparticles (GNPs) were studies as the carrier of SAHM1 in penetrating into Jurkat cells in order to enhance antiproliferative activity of SAHM1. GNPs were synthesized by reaction between trisodium citrate and HAuCl4 at different conditions to obtain the particles with the averaged size of 20 nm, 40 nm and 60nm. SAHM1 was attached to the GNPs using thiolated polyethylene glycol (PEG) as the linker. Cytotoxicity of GNPs, thiolated PEG, thiolated PEG-GNPs, SAHM1 and SAHM1-(thiolated PEG)-GNPs was investigated by conventional MTT assay. Cell viabilities of Jurkat cells decreased to about 70% when separately treated with GNPs, SAHM1 and thiolated PEG-GNPs as compared to those of the untreated cells. Cell viabilities of the cell treated with SAHM1-GNPs noticeably decreased only when 20 nm GNPs coated with 62.5 µM and 125 µM SAHM1 were used as compared to those of cells treated with GNPs, thiolated PEG, thiolated PEG-GNPs and SAHM1. Therefore, enhancement of antiproliferative activity of SAHM1 was found when 20 nm GNPs coated with 62.5 µM and 125 µM SAHM1 were used. Study of mode of program cell death by staining cells with Annexin V and propidium iodide after cell treatment with SAHM1-GNPs for 24 h and 48 h revealed that most cells died in early apoptosis and late apoptosis.