Abstract
AbstractNeuronal differentiation promoted by protein delivery is a promising strategy for the treatment of neuropathies. Herein, alkaline earth metal (AEM)‐doped hollow nanoparticles (HNPs) are utilized for simultaneous delivery of metal ions and nerve growth factor (NGF) toward cell interiors via endocytosis. Various AEMs including Mg, Ca, Sr, and Ba are readily doped onto the HNPs and the resulting AEM‐HNPs serve as NGF delivery agents. Benefiting from the hollow morphology, NGFs are successfully loaded into AEM‐HNPs to obtain NGF‐loaded N+AEM‐HNPs. These are applied as neuronal development agents for PC12 cells, a model for neuronal development experiments. The neuronal development efficiency of PC12 is improved in the presence of all N+AEM‐HNPs. Notably, the AEM‐HNPs manifest neuronal development effects that depend on the identity of the AEMs. Specifically, by studying the protein expressions and their signal transduction pathways, it is found that PC12 cells are activated by different signaling cascades according to each AEM ions. Additionally, Mg/Sr‐HNPs containing both Mg2+ and Sr2+ ions are prepared to examine the effect of dual stimulation of AEM ions on PC12 cells. This novel dual‐delivery system provides new insights into the synergistic neuronal development effect of AEM ions and protein in a single system.
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