Epidermal growth factor receptors siRNA-conjugated collagen modified gold nanoparticles for targeted imaging and therapy of lung cancer

Epidermal growth factor receptor (EGFR), a critical factor promotes lung cancer cell proliferation and survival. Knockdown of EGFR expression thus promise beating lung cancer clinically. Functionalized gold nanoparticles may serve an effective vehicle carrying theranostic bio-active materials. Herein, physically gold nanoparticles were fabricated with biocompatible collagen to improve siRNA loading capacity carrying EGFR siRNA to treat lung cancer. Physic-chemical properties were comprehensively characterized for the collagen gold nanoparticle (C–Au), and with EGFR siRNA conjugation, C–Au-EGFRsi namely. Issues of biocompatibility were addressed. Interestingly, C–Au appeared more biocompatible to normal airway epithelial cells (BEAS-2B) than to cancer cells (A549) in terms of ROS production, cell cycle behavior, and cell growth influence. The C–Au demonstrated comparable or even more efficient, compared with lipofetamine, in carrying siRNA to knockdown EGFR of A549 cells. Endocytosis mediated cell entry for the collagen gold nanoparticles, and endosome-lysosomal pathway involved transporting and metabolizing these nanoparticles. In xenograft mice model, substantial tumor suppression effects were observed treating with C–Au-EGFRsi, in which tumor weight reduced 30% for lipofetamine carrier, and down to 70% for C–Au carrier. Particularly, overall survival rate was improved for both treatment groups with lipofetamine and C–Au carrier, respectively. Graph Abstract. Scheme diagram of using physical nanogold, decorated with collagen, to carry EGFR siRNA achieving in vitro, in vitro, inhibition effects for A549 lung cancer. A549 cells were inoculated in nude mice at flank region for tumor growing, then intraperitoneally administered EGFR siRNA, carried by lipofetamine and C–Au nanocarriers, at day 1, day 3, and day 7. Mice were sacrificed at day 30 to excise the growing tumor for subsequent survey (A). For in vitro study, we used cell model, A549 and BEAS-2B, to examine the biocompatibility and explore the potential inducing apoptosis/death for the collagen gold nanoparticles (B). In summary, we used a novel collagen gold nanoparticle carring EGFR siRNA in attempt to treat lung cancer and the results were promising. This C–Au-EGFRsi in vitro induced survival stress to A549 resulting apoptosis/death and inhibiting invasion, which was relatively biocompatible to BEAS-2B cells, however. In mice xenograft tumor bearing model, intraperitoneally administered at day 1, 3