Nanoparticle delivery of curcumin induces cellular hypoxia and ROS-mediated apoptosis via modulation of Bcl-2/Bax in human neuroblastoma

作者：Kalashnikova Irina; Mazar Joseph; Neal Craig J; Rosado Amy L; Das Soumen; Westmoreland Tamarah J; Seal Sudipta^*

来源：Nanoscale, 2017, 9(29): 10375-10387.

DOI：10.1039/c7nr02770b

In this study, several formulations of nanoceria and dextran-nanoceria with curcumin, each demonstrated to have anti-cancer properties, were synthesized and applied as treatment for human childhood neuroblastoma. The anti-cancer activities of these formulations were explored in neuroblastoma models of both MYCN-amplified and non-amplified cell lines. Ceria nanoparticles, coated with dextran and loaded with curcumin, were found to induce substantial cell death in neuroblastoma cells (up to a 2-fold and a 1.6-fold decrease in cell viability for MYCN-upregulated and normal expressing cell lines, respectively; (star)p < 0.05) while producing no or only minor toxicity in healthy cells (no toxicity at 100 mu M; (star star)p < 0.01). This formulation evokes prolonged oxidative stress, stabilizing HIF-1 alpha, and inducing caspase-dependent apoptosis (up to a 2.4-fold increase over control; (star)p < 0.05). Overall, nano-therapeutic treatments showed a more pronounced effect in MYCN-amplified cells, which are traditionally more resistant to drug therapies. These results represent a very promising alternative to small molecule drug therapies for robust cancers.

• 出版日期2017-8-7