Promoted delivery of salinomycin sodium to lung cancer cells by dual targeting PLGA hybrid nanoparticles.

Abstract

As the leading cause of cancer-associated mortality worldwide, lung cancer is often associated with therapy failure and decreases in survival; these factors are often attributed to lung cancer-initiating cells (CICs). In addition, sufficient evidence has suggested that simultaneous targeting of CICs, together with cancer cells, is critical for the achievement of preferable therapeutic efficacy, due to the spontaneous conversion between CICs and cancer cells. Salinomycin sodium(SS) is an antibacterial therapeutic agent that exerts potent activity against CICs in various types of cancer, including lung cancer. The present study generated SS lipid-polymer hybrid nanoparticles(NPs) with cluster of differentiation(CD)133 and epidermal growth factor receptor (EGFR) antibodies (CD133/EGFRSSNPs) for the simultaneous treatment of lung CICs and cancer cells. The activity of CD133/EGFRSSNPs was analyzed using cytotoxicity and tumorsphere formation assays, flow cytometry, and an in vivo anticancer assay in mice bearing lung cancer xenografts. The results revealed that CD133/EGFRSSNPs effectively promoted SS delivery to lung CICs and cancer cells, achieving superior therapeutic effects compared with non-targeted NPs or NPs with a single antibody. Furthermore, CD133/EGFRSSNPs exhibited the best efficacy in inhibiting tumor growth compared with the control agents in lung cancer-bearing mice. In conclusion, CD133/EGFRSSNPs may be capable of efficiently targeting and treating lung CICs together with cancer cells, and may represent an effective treatment for lung cancer.