Polymeric nanoparticle‐based delivery of TRAIL DNA for cancer‐specific killing

Lack of specificity in cancer therapeutics severely limits the efficacy of many existing treatment modalities. The use of Tumor Necrosis Factor‐related Apoptosis‐Inducing Ligand (TRAIL) is of interest to the field due to this protein's ability to cause cell death specifically in cancer cells without harming the surrounding healthy tissue. Here, we report that polymeric nanoparticles, based on synthetic poly(beta‐amino ester)s (PBAEs) and containing DNA, are able to selectively transfect cancer cells in vitro over healthy cells of the same tissue type. Moreover, PBAE‐based nanoparticles containing TRAIL DNA are able to transfect several human cancer cell cultures in vitro and cause cell death. While certain cell types, including human glioblastoma (GBM), showed resistance to TRAIL, we found that the expression of TRAIL‐binding surface proteins was predictive of each cell type's resistance to TRAIL therapy. We demonstrate a non‐viral nanomedicine approach to cancer gene therapy that can improve cancer specificity via both biomaterial selection and through the use of cancer‐targeting genetic cargo.