165 / 2024-06-13 19:39:56

Multimodal nanoplatform for dynamic monitoring and targeting drug delivery allowing penetration of blood brain barrier

Mesenchymal stem cells, blood brain barrier, core shell nanoparticles, NIR/Vis dyes, inflammation tropism, LPS-induced neuroinflammation mouse model.

Mesenchymal stem cells (MSCs) have certain innate homing ability toward the site of inflammation and have thus gained more attention as vehicles for targeted neuroinflammation therapy. The objective of the study was to create a novel, active, and multifunctional nanoplatform (stem cells loaded with nanoparticles (NPs) and NIR/visible dye) by using mouse bone marrow derived mesenchymal stem cell (MSCs) as a carrier for biodistribution and inflammation tropism of this nanoplatform in lipopolysaccharides (LPS)-induced neuroinflammation mouse model after crossing the blood brain barrier (BBB) which is the complex and selective diffusion barrier. In this work, core-shell polymeric NPs are synthesized and loaded with near infrared (NIR) and visible fluorescent dyes for internalization into MSCs (MSCs/NIR-NP or MSCs/Vis-NP, respectively). Dynamic light scattering (DLS) is used for the analysis of changes in the size of NPs depending on temperature. The fluorescent intensity of the dyes (NIR/visible) in different solvents was analyzed with fluorescence spectrometry. The capability of the nanoplatform to distribute and selectively target brain inflammation site was investigated in LPS-induced neuroinflammation mouse model by intravenous and intracranial injections. Moreover, the migratory potential and tissue targeting ability of MSCs/NIR-NP and MSCs/Vis-NP were systematically compared at various levels, which include in vitro, ex vivo, and in situ. Furthermore, the in vivo inflammation targeting property of MSCs/NIR-NP was explored using NIR fluorescence imaging. In vitro, there is no cytotoxicity or changes in morphology of MSCs with NPs at the investigated concentrations compared to the control MSCs. In vivo, MSCs with NPs with NIR/visible dyes can readily penetrate BBB and accumulate at the site of inflammation in the brain. This demonstrates the utility of our multifunctional nanoplatform for dynamic tracking and on-demand drug delivery in neurological diseases, highlighting the necessity and efficacy of overcoming BBB.