Table 5.

Selected relevant pre-clinical studies based on recent MNPs for the diagnosis and treatment of AD

Loaded molecule	Metal core	Surface modifications	Dose	Admin. route	In vitro/in vivo Model	Results	Refs
–	Iron oxide	NIR Fluorescent probe	10 ng/mL	Incubation	Aβ42 induced SH-SY5Y cells	MNPs can simultaneously perform in vivo NIR fluorescence and magnetic resonance imaging of Aβ plaques in the brain of transgenic mice, prevent Aβ aggregation, disaggregate preformed Aβ fibrils and play a protective effect on the toxicity of human neuroblastoma cells induced by Aβ42	Cai et al. [201]
			0.2 mmol Fe/kg	i.v	APP/PS1 mice
–	Iron oxide	chitosan	NA	Exposition	Synthetic urine	MNPs were used to fabricate a highly sensitive AChE electrochemical biosensor. The novel biosensor exhibits the lower limit of detection of ACh that has been reported in the literature. It also shows good recoveries in the determination of ACh in synthetic urine	da Silva et al. [192]
–	Selenium	Chondroitin sulfate	1.45 µg/mL	Incubation	SH-SY5Y cells	MNPs inhibit Aβ aggregation, protect SH-SY5Y cells from Aβ42-induced cytotoxicity, decrease okadaic acid-induced actin cytoskeleton instability, In addition, decrease the levels of ROS and MDA, increase the levels of GSH-Px, and attenuate the hyperphosphorylation of tau by regulating the expression of GSK-3b	Gao et al. [195]
–	Cerium dioxide	Zirconium	4 mg/m3 for 3–5 h/day	i.n	5xFAD mice ApoE-/- mice	The inhalation exposure to the MNPs promotes changes in forced motor performance and exploratory motor activity in ApoE-/- and 5xFAD mice, respectively	Wahle et al. 2020
Quercetin	Gold / Palladium	Polysorbate 80	5–40 µg/mL	Incubation	SH-SY5Y cells	MNPs activate autophagy of SH-SY5Y cells, promote the fusion of autophagosomes and lysosomes, accelerate the clearance of Aβ, and protect SH-SY5Y cells from Aβ -induced cytotoxicity damage. MNPs are not toxic both in vitro and in vivo	Liu et al. [194]
			1 mg/kg	i.v	Nude mice
–	Iron oxide Cadmium sulfide	F. oxysporum and Verticillium sp. proteins	5 − 100 μg/mL	incubation	Neuro2a cells	MNPs do not affect the viability of neuroblastoma cells and show dual properties of inhibition and disaggregation of Tau fibrillar aggregates	Sonawane et al. [198]
–	Palladium	Bioactive Hydrogen	6.25–25 µg/ml	incubation	N2a-SW cells	Developed MNPs are able to recover mitochondrial dysfunction, inhibit Aβ generation and aggregation, block synaptic and neuronal apoptosis and promote neuronal energy metabolism by eliminating oxidative stress and activating the anti-oxidative pathway, consequently ameliorating the cognitive impairment in AD mice	Zhang et al. [200]
			2µL of MNPs (0.5–2 mg/ml)	Stereotaxic injection	APP/PS1 mice
–	Silver	PrP95-110	1.2 nM	Incubation	Aβ enriched CSF and serum	Authors report an electrochemical method for the detection of Aβ oligomer with a peptide as the bio-receptor and silver MNPs aggregates as the redox reporters	Xing et al. [193]
CQ	Gold	–	0.5 mg/mL	Incubation	PC12 cells	In this system, CQ is released only upon exposure to conditions in which H2O2 levels are high, such as those in Aβ plaques. NPs inhibit Aβ40 aggregation, and reduce the cell membrane disruption, microtubular defects and ROS-mediated apoptosis	Yang et al. [199]
			5, 10, 20 mg/kg	i.v	ICR mice

Ach, acetylcholine; CQ, metal chelator Clioquinol; CSF, cerebrospinal fluid; GSH-Px, glutathione peroxidase; MDA, malondialdehyde; NIR, phenothiazine-based near-infrared fluorescent dye; PrP_95-110, cellular prion protein; ROS, reactive oxygen species; STZ, streptozotocin