Co-delivery of Salinomycin and Curcumin for Cancer Stem Cell Treatment by Inhibition of Cell Proliferation, Cell Cycle Arrest, and Epithelial–Mesenchymal Transition

Abstract

Malignant cancer is a devastating disease often associated with a poor clinical prognosis. For decades, modern drug discoveries have attempted to identify potential modulators that can impede tumor growth. Cancer stem cells however are more resistant to therapeutic intervention, which often leads to treatment failure and subsequent disease recurrence. Here in this study, we have developed a specific multi-target drug delivery nanoparticle system against breast cancer stem cells (BCSCs). Therapeutic agents curcumin and salinomycin have complementary functions of limiting therapeutic resistance and eliciting cellular death, respectively. By conjugation of CD44 cell-surface glycoprotein with poly(lactic-co-glycolic acid) (PLGA) nanoparticles that are loaded with curcumin and salinomycin, we investigated the cellular uptake of BCSCs, drug release, and therapeutic efficacy against BCSCs. We determined CD44-targeting co-delivery nanoparticles are highly efficacious against BCSCs by inducing G1 cell cycle arrest and limiting epithelial–mesenchymal transition. This curcumin and salinomycin co-delivery system can be an efficient treatment approach to target malignant cancer without the repercussion of disease recurrence.

M1 Macrophage-Derived Exosomes Loaded with Gemcitabine and Deferasirox against Chemoresistant Pancreatic Cancer

“…Wound healing study was carried out using our method as previously described [ 30 ]. In brief, cells were seeded in 96-well plates and cultured until they reached more than 80% confluence and incubated in serum-free medium to eliminate the effect of cell proliferation.…”

Targeting NF-κB Signaling in Cancer Stem Cells: A Narrative Review

“…There is some published pre-clinical evidence for salinomycin targeting NF-κB [ 44 , 63 , 64 , 65 , 66 ]. Furthermore, salinomycin and another natural compound: curcumin, making a yellow color in curry, were used as a magic bullet to target stem-cell specific receptor CD44 with a synthetic ligand [ 67 ]. Another interesting strategy to identify NF-κB-inhibiting substances by screening clinically approved small molecules was used by the NIH Chemical Genomics Center [ 68 ].…”

Salinomycin-Based Drug Delivery Systems: Overcoming the Hurdles in Cancer Therapy

“…The hyaluronic acid-coupled nanoparticles promoted the G1/S cell cycle arrest, leading to subsequent apoptosis of breast CSCs. This suggests that hyaluronic acid-conjugated nanoparticles are a promising means of selectively delivering Sali and curcumin to breast CSCs [ 80 ].…”