Functionalization of single-walled carbon nanotubes enables efficient intracellular delivery of siRNA targeting MDM2 to inhibit breast cancer cells growth

Abstract

The delivery of DNA or RNA to cells represents the limiting step in the development of cancer gene therapy and RNA interference protocols. Single walled carbon nanotubes (SWNTs) are of interest as carriers of biologically active molecules because of their ability to cross cell membranes. In this study, we developed a novel strategy for chemical functionalization of SWNTs (f-SWCNTs) with DSPE-PEG-Amine to bind small interfering RNA (siRNA) by disulfide bonds applied to siRNA-mediated gene silencing in breast cancer cells. Results indicated the efficiency of f-SWNTs carrying siRNA reached 83.55%, and the new f-SWNTs-siRNA-MDM2 complexes were successfully introduced into the breast carcinoma B-Cap-37 cells at a concentration of 100nM in mediums, and caused proliferation inhibition of B-Cap-37 cells significantly. The proliferation inhibition ratio of B-Cap-37 cells was detected as 44.53% for 72h, and the apoptosis ratio was measured as 30.45%. It was obvious that MDM2 can serve as a novel therapeutic target by an effective carrier system of DSPE-PEG-Amine-functionalized SWNTs, which would be very advanced and significant to therapy of breast cancer further.