Anti-breast cancer effects of free and nanocarrier-loaded salinomycin and doxorubicin

n: Salinomycin (SAL) and doxorubicin (DOX) have previously garnered much attention as anticancer drugs. However, their encapsulation within a nanocarrier dendrosome and their possible synergistic effect have not been reported, which we aim to address. SAL and DOX were loaded into the produced OA400 nanocarrier. Then, their effects on cell viability, apoptosis, migration, and invasion were analyzed in MDA-MB-231 and MCF-7 cells. The evaluations were conducted using MTT, flow cytometry, scratch, and Matrigel tests. The treatments were performed with encapsulated and free forms of the individual drugs, and in combination. The miRNAs Let-7, miR-21, miR-10b, and miR-128 expression was assessed by qRT-PCR to evaluate the cellular effects of the treatments. The results showed that the combination of free SAL and DOX and the combination of SAL and DOX loaded in OA400 were more effective than their treatment as singular drugs in the inhibition of proliferation and induction of apoptosis. The expression of miRNAs, miR-21 and miR-10b, the most important tumor miRNAs, was decreased, and the expression of Let-7, an inhibitor of tumor growth, was increased. However, miR-128 expression didn't change significantly. The nanocarrier OA400 provides a potential strategy for targeted delivery of SAL and DOX, providing a sustained release profile. Moreover, combined administration of these drugs showed a synergistic anticancer activity, which could be deemed as an effective anti-cancer therapy against breast cancer. Despite the obtained promising results, further in vivo studies would shed light on the true potential of this strategy.