The effect of hyaluronic acid functionalized carbon nanotubes loaded with salinomycin on gastric cancer stem cells

Abstract

Gastric cancer stem cells (CSCs) play a crucial role in the initiation, development, relapse and metastasis of gastric cancer because they are resistant to a standard chemotherapy and the residual CSCs are able to proliferate indefinitely. Therefore, eradication of this cell population is a primary objective in gastric cancer therapy. Here, we report a gastric CSCs-specifically targeting drug delivery system (SAL-SWNT-CHI-HA complexes) based on chitosan(CHI) coated single wall carbon nanotubes (SWNTs) loaded with salinomycin (SAL) functionalized with hyaluronic acid (HA) can selectively eliminate gastric CSCs. Gastric CSCs were identified as CD44+ cells and cultured in serum-free medium. SAL-SWNT-CHI-HA complexes were capable of inhibiting the self-renewal capacity of CD44+ population, and decrease mammosphere- and colon-formation of CSCs. In addition, the migration and invasion of gastric CSCs were significantly blocked by SAL-SWNT-CHI-HA complexes. Quantitative and qualitative analysis of cellular uptake demonstrated that HA functionalization facilitated the uptake of SWNTs in gastric CSCs while free HA competitively inhibited cellular uptake of SAL-SWNT-CHI-HA delivery system, revealing the mechanism of CD44 receptor-mediated endocytosis. The SAL-SWNT-CHI-HA complexes showed the strongest antitumor efficacy in gastric CSCs by inducing apoptosis, and in CSCs mammospheres by penetrating deeply into the core. Taken altogether, our studies demonstrated that this gastric CSCs-targeted SAL-SWNT-CHI-HA complexes would provide a potential strategy to selectively target and efficiently eradicate gastric CSCs, which is promising to overcome the recurrence and metastasis of gastric cancer and improve gastric cancer treatment.