Dual targeting of a thermosensitive nanogel conjugated with transferrin and RGD-containing peptide for effective cell uptake and drug release

In this paper, both arginine-glycine-aspartic acid (RGD)-containing peptide and transferrin (Tf) were conjugated to the thermosensitive poly(N-isopropylacrylamide-co-propyl acrylic acid) (poly(NIPAAm-co-PAAc)) nanogel to prepare a dual-targeting drug carrier. The obtained nanogel was characterized in terms of fluorescence spectroscopy, UV-vis spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM). In order to track the dual-ligand conjugated nanogel, fluorescein isothiocyanate (FITC) was further conjugated to the nanogel. A cell internalization experiment showed that the dual-ligand conjugated nanogel exhibited obviously enhanced endocytosis by HeLa cells as compared with non-tumorous cells (COS-7 cells). The drug-loaded dual-ligand conjugated nanogel could be transported efficiently into the target tumor cells and the anti-tumor effect was enhanced significantly, suggesting that the dual-ligand conjugated nanogel has great potential as a tumor targeting drug carrier.