Carbon dot festooned and surface passivated graphene-reinforced chitosan construct for tumor-targeted delivery of TNF-α gene.

Gene therapy is a promising alternative that ensures effective treatment and cure for cancer. Here, we report graphene-reinforced chitosan (CS) construct based non-viral vector for tumor-targeted gene therapy. The therapeutic gene, pDNA-TNF-α, was loaded on to chitosan-carboxylated graphene oxide (CS-CGO) construct via electrostatic interaction. The pDNA-TNF-α-CS-CGO thus obtained was further passivated with 4,7,10-trioxa-1,13-tridecanediamine for protecting the vector from the mononuclear phagocyte system that contributes to the prolongation of circulation half-life. The surface passivated carrier (PEG-pDNA-TNF-α-CS-CGO) then festooned with the folic acid derived carbon dots (C-dots) for targeting folate receptors that are overexpressed in most of the cancer cells. The results of TEM images and zeta potential values ensured the occurrence of desired changes in each stage of C-dot-PEG-pDNA-TNF-α-CS-CGO formulation. After 14 days of incubation, the anti-angiogenesis effect was observed for final formulation in the chorioallantoic membrane. The results of in vitro gene expression study in cancer cell line show a comparatively higher transfection efficacy of the developed system (C-dot-PEG-pDNA-TNF-α-CS-CGO) than pDNA-TNF-α. The efficiency of the developed gene delivery system was further confirmed using a developed and validated artificial tumor cell apparatus.