Lung cancer targeted therapy: Folate and transferrin dual targeted, glutathione responsive nanocarriers for the delivery of cisplatin

•Nanoparticles, which are glutathione (GSH) responsive, are designed to disassemble and release drugs in the cytoplasm in which the concentration of glutathione is higher than in the plasma.•Covalent conjugation of FA or Tf could enhance specificity uptake of NPs in the tumor area, where receptors are over-expressed.•The modified NPs may target the tumor cells, delay the drug release and bring about the long-lasting drug delivery effect in tumor tissues. To achieve lung cancer targeted therapy, folic acid (FA) and transferrin (Tf) modified cisplatin (CDDP) loaded nanoparticles were applied for the in vitro and in vivo evaluation. The aim of this research was to develop FA modified SS bonds based prodrug of CDDP (namely FA-ss-CDDP) and Tf modified cystamine-oleic acid (Tf-ss-OA). Further, FA-ss-CDDP and Tf-ss-OA were used to prepare NPs, which could target the lung tumor cells through receptor-mediated pathways to increase the efficiency of CDDP. FA and Tf modified CDDP loaded NPs (FA/Tf-CDDP-NPs) were constructed. The physiochemical properties, in vitro drug release profiles, in vitro cytotoxicity, and in vivo biodistribution were investigated. The antitumor effect of self-assembed NPs was evaluated both in vitro and in vivo. FA/Tf-CDDP-NPs exhibited remarkably enhanced accumulation in tumor tissue and better tumor inhibition effect in vitro and in vivo. FA/Tf-CDDP-NPs displayed almost complete suppression of tumor growth with no obviously body weight change of the treated mice. The newly constructed NPs could successfully load drugs and showed better efficiency than free drug formula; and FA/TF could function as excellent targeting ligands to improve the cell targeting ability of the NPs. The resulting FA/Tf-CDDP-NPs offered a promising tumor therapy strategy for the treatment of lung cancer.