Targeted lung cancer therapy: preparation and optimization of transferrin-decorated nanostructured lipid carriers as novel nanomedicine for co-delivery of anticancer drugs and DNA

• Main Authors: Shao Z, Shao J, Tan B, Guan S, Liu Z, Zhao Z, He F, Zhao J
• Format: Article
• Language: English
• Published: Dove Medical Press 2015-02-01
• Series: International Journal of Nanomedicine
• Online Access: http://www.dovepress.com/targeted-lung-cancer-therapy-preparation-and-optimization-of-transferr-peer-reviewed-article-IJN

Zhenyu Shao,1 Jingyu Shao,2 Bingxu Tan,1 Shanghui Guan,1 Zhulong Liu,1 Zengjun Zhao,1 Fangfang He,1 Jian Zhao3 1Department of Radiotherapy, Cancer Centre, Qilu Hospital, Shandong University, Ji’nan, Shandong, People’s Republic of China; 2Affiliated Hospital of Northwest Institute of Mechanical and Electrical Engineering, Xianyang, Shaanxi, People’s Republic of China; 3Department of Thoracic Surgery, Qilu Hospital, Shandong University, Ji’nan, Shandong, People’s Republic of China Purpose: Nanostructured lipid carriers (NLC) represent an improved generation of lipid nanoparticles. They have specific nanostructures to accommodate drugs/genes, and thus achieve higher loading capacity. The aim of this study was to develop transferrin (Tf)-decorated NLC as multifunctional nanomedicine for co-delivery of paclitaxel (PTX) and enhanced green fluorescence protein plasmid.Methods: Firstly, Tf-conjugated ligands were synthesized. Secondly, PTX- and DNA-loaded NLC (PTX-DNA-NLC) was prepared. Finally, Tf-containing ligands were used for the surface decoration of NLC. Their average size, zeta potential, drug, and gene loading were evaluated. Human non-small cell lung carcinoma cell line (NCl-H460 cells) was used for the testing of in vitro transfection efficiency, and in vivo transfection efficiency of NLC was evaluated on mice bearing NCl-H460 cells.Results: Tf-decorated PTX and DNA co-encapsulated NLC (Tf-PTX-DNA-NLC) were nano-sized particles with positive zeta potential. Tf-PTX-DNA-NLC displayed low cytotoxicity, high gene transfection efficiency, and enhanced antitumor activity in vitro and in vivo.Conclusion: The results demonstrated that Tf-PTX-DNA-NLC can achieve impressive antitumor activity and gene transfection efficiency. Tf decoration also enhanced the active targeting ability of the carriers to NCl-H460 cells. The novel drug and gene delivery system offers a promising strategy for the treatment of lung cancer. Keywords: co-delivery, nanostructured lipid carriers, transferrin decoration, active targeting systems, paclitaxel