Transfection of the TRAIL gene into human mesenchymal stem cells using biocompatible polyethyleneimine carbon dots for cancer gene therapy

For effective gene therapy using Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL), which is a protein that selectively induces cancer cell apoptosis through human mesenchymal stem cells (hMSCs), low cytotoxicity branched polyethyleneimine (bPEI) 25k carbon dots (bPEI25k CDs) were investigated as a TRAIL–GFP gene (plasmid TRAIL–GFP, pTRAIL–GFP) carrier for delivery into hMSCs. bPEI25k CDs were prepared using one-step microwave-assisted pyrolysis, which has the advantage of low cytotoxicity and allows for bioimaging after gene delivery. The bPEI25k CDs had lower cytotoxicity levels at all tested concentrations, whereas the raw bPEI25k were cytotoxic in proportions up to a concentration by 25%. The complex containing bPEI25k CDs and pTRAIL–GFP was safely internalized and transfected into the hMSCs. It also revealed a cellular fluorescence imaging property induced by a unique characteristic of CDs. The amount of secreted TRAIL from bPEI25k CDs/pTRAIL–GFP@hMSCs was 25-fold higher than that from bPEI25k/pTRAIL–GFP@hMSCs, leading to a higher cytotoxic effect against the lung cancer cells. Therefore, bPEI25k CDs are recommended as an effective gene carrier for successful cancer gene therapy mediated through hMSCs.