Osteosarcoma is a common childhood bone cancer with a poor survival rate. Osteosarcoma cancer stem cells (CSCs) contribute to the recurrence, drug resistance and metastasis of this disease. Previous evidence suggested that cancer cells are able to spontaneously turn into CSCs, thus it is crucial to simultaneously target osteosarcoma cells and CSCs. Our previous studies have demonstrated that salinomycin preferably eliminated osteosarcoma CSCs. In addition, amplification of the epidermal growth factor receptor (EGFR) is a common genetic aberration in osteosarcoma, and thus EGFR is a promising target in osteosarcoma. The present study aimed to develop EGFR aptamer‑conjugated salinomycin‑loaded polymer‑lipid hybrid nanoparticles (EGFR‑SNPs) to target both osteosarcoma cells and CSCs. The results revealed that EGFR was overexpressed in these cells, and that EGFR‑SNPs possessed a small size of 95 nm, suitable drug encapsulation efficiency (63%) and sustained drug release over 120 h. EGFR‑SNPs targeted EGFR‑overexpressing osteosarcoma cells and CSCs, resulting in an enhanced cytotoxic effect compared with non‑targeted SNPs and salinomycin. Notably, EGFR‑SNPs was able to reduce the osteosarcoma tumorsphere formation rate and proportion of CD133+ osteosarcoma CSCs in the osteosarcoma cell lines more effectively compared with SNPs and salinomycin, suggesting that EGFR‑SNPs effectively reduced the proportion of osteosarcoma CSCs. In conclusion, the interaction of EGFR aptamers and EGFR is a potential approach to promote the effective delivery of salinomycin to osteosarcoma. The study results suggested that EGFR‑SNPs represents a promising approach to target osteosarcoma cells and CSCs.

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