Design and fabrication of dual‐targeted delivery system based on gemcitabine‐conjugated human serum albumin nanoparticles

Dual‐targeted drug delivery system has established their reputation as potent vehicles for cancer chemotherapies. Herein, gemcitabine (Gem) was conjugated to human serum albumin (HSA) via dithiodipropionic anhydride to fabricate Gem‐HSA nanoparticles. It was hypothesized that this system can enhance the low stability of Gem and can improve its intracellular delivery. Furthermore, folate was applied as targeting agent on HSA nanoparticles for increasing the tumor selectivity of Gem. To evaluate the structural properties of synthesized products, 1H NMR and FT‐IR were performed. Moreover, HPLC was implemented for confirming the conjugation between HSA and Gem. Nanoparticles have shown spherical shape with negative charge. The release rate of Gem was dependent to the concentration of glutathione and pH. Folate‐targeted HSA nanoparticles have shown higher cytotoxicity, cellular uptake, and apoptosis induction on folate receptor overexpressing MDA‐MB‐231 cells in comparison to non‐targeted nanoparticles. Finally, it is considered that the developed dual‐targeted nanoparticles would be potent in improving the stability and efficacy of intracellular delivery of Gem and its selective delivery to cancer cells. In this study, we prepared folate‐targeted Gem‐HSA nanoparticles. Dithiodipropionic anhydride disulfide linker was used to conjugate Gem with HSA. Nanoparticles had spherical shape and negative charge. Release rate of Gem from nanoparticles was accelerated under reductive and acidic pH. Folate targeting of nanoparticles improved the cytotoxicity, cellular uptake, and apoptosis induction of nanoparticles. The dual‐targeted nanoparticles enhanced the stability and efficacy of Gem by intracellular release and selective delivery to cancer cells.