Mesoporous silica nanoparticles (MSNs) have gained wide attention for their role in biomedicine and as drug delivery vehicles. Their structural tunability, high surface area, and easy functionalization impart significant advantages over conventional materials. In this Review, recent advances in the synthesis, drug delivery, and therapeutic roles of MSNs in the treatment of various neurodegenerative and neuroinflammatory diseases are presented. The intention is to understand how MSN formulations that are capable of encapsulating drug molecules can enhance drug delivery by overcoming the blood–brain barrier (BBB) mediated by specific transport processes. The composition and characteristics of the BBB, and how alterations are observed in neurodegenerative diseases including Alzheimer's, epilepsy, and intracerebral hemorrhage are reviewed. Finally, the factors affecting efficient delivery of MSNs into the brain are summarized, and their most promising functional outcomes are discussed.

We designed and synthesized novel theranostic nanoparticles that showed the considerable potential for clinical use in targeted therapy, and non-invasive real-time monitoring of tumors by MRI. Our nanoparticles were ultra-small with superparamagnetic iron oxide cores, conjugated to erlotinib (FeDC-E NPs). Such smart targeted nanoparticles have the preference to release the drug intracellularly rather than into the bloodstream, and specifically recognize and kill cancer cells that overexpress EGFR while being non-toxic to EGFR-negative cells. MRI, transmission electron microscopy and Prussian blue staining results indicated that cellular uptake and intracellular accumulation of FeDC-E NPs in the EGFR overexpressing cells was significantly higher than those of the non-erlotinib-conjugated nanoparticles. FeDC-E NPs inhibited the EGFR–ERK–NF-κB signaling pathways, and subsequently suppressed the migration and invasion capabilities of the highly invasive and migrative CL1-5-F4 cancer cells. In vivo tumor xenograft experiments using BALB/c nude mice showed that FeDC-E NPs could effectively inhibit the growth of tumors. T₂-weighted MRI images of the mice showed significant decrease in the normalized signal within the tumor post-treatment with FeDC-E NPs compared to the non-targeted control iron oxide nanoparticles. This is the first study to use erlotinib as a small-molecule targeting agent for nanoparticles.

Mesenchymal stem cells (MSCs) are emerging as a potential therapeutic intervention for brain injury due to their neuroprotective effects and safe profile. However, the homing ability of MSCs to injury sites still needs to be improved. Fibroblast Growth Factor 21 (FGF21) was recently reported to enhance cells migration in different cells type. In this study, we investigated whether MSCs that overexpressing FGF21 (MSC-FGF21) could exhibit enhanced homing efficacy in brain injury. We used novel Molday IONEverGreen™ (MIEG) as cell labeling probe that enables a non-invasive, high-sensitive and real-time MRI tracking. Using a mouse model of traumatic brain injury (TBI), MIEG labeled MSCs were transplanted into the contralateral lateral ventricle followed by real-time MRI tracking. FGF21 retained MSC abilities of proliferation and morphology. MSC-FGF21 showed significantly greater migration in transwell assay compared to control MSC. MIEG labeling showed no effects on MSCs’ viability, proliferation and differentiation. Magnetic resonance imaging (MRI) revealed that FGF21 significantly enhances the homing of MSC toward injury site. Histological analysis further confirmed the MRI findings. Taken together, these results show that FGF21 overexpression and MIEG labeling of MSC enhances their homing abilities and enables non-invasive real time tracking of the transplanted cells, provides a promising approach for MSC based therapy and tracking in TBI.