Nanoparticles with Multiple Enzymatic Activities Purified from Groundwater Efficiently Cross the Blood-Brain Barrier, Improve Memory, and Provide Neuroprotection

Many engineered nanomaterials (ENMs) and drugs have been fabricated to improve memory and promote neuroprotection, but their use remains challenging due to their high cost, poor ability to penetrate the blood-brain barrier (BBB), and many side effects. Herein, we found that nanoparticles with multiple enzymatic activities purified from groundwater (NMEGs) can efficiently cross the BBB and present memory-enhancing and neuroprotective effects in vitro and in vivo. In contrast to the adverse effects of chemicals and ENMs, NMEGs are able to cross the BBB by endocytosis without damaging the BBB and even possibly promote BBB integrity. NMEGs-treated normal mice were smarter and better behaved than salinetreated normal mice in the open-field test and Morris water maze test. NMEGs can enhance synaptic transmission by increasing neurotransmitter production and activating nicotinic acetylcholine receptors (nAChRs), activate the antioxidant enzyme system, and increase the number of mitochondria and ribosomes in cells. Intravenous NMEGs injection also rescued memory deficits and increased antioxidant capacity in Parkinson's disease (PD) mice due to the antioxidant activity caused by the presence of conjugated double bonds and abundant phenolic -OH groups. This study is a proof-of-principle demonstration that natural products are less expensive, more easily available, safer, and more effective ways to improve memory and promote neuroprotection than ENMs and reported drugs. Our article also shows the potential of NMEGs as a PD treatment in patients via intravenous injection, as they avoid the complex modifications of ENMs. In the future, it will be possible to treat PD by intravenously injecting NMEGs in patients.