Mesoporous Silica Nanoparticles for Targeted Aβ₄₂ Imaging and Therapy in Traumatic Brain Injury: Enhanced Blood–Brain Barrier Penetration and Sustained Drug Delivery

The focus of the study lies in the design of functionalized mesoporous silica nanoparticles with the aim toward enhanced permeability across the blood-brain barrier while ensuring effective binding to Aβ42 aggregates. Chalcone and diethylenetriamine pentaacetic acid (DTPA) functionalized mesoporous silica nanoparticles, MSN-DTPA-Chal, were characterized via field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM), which displayed spherical morphology and homogeneous size distribution (48 ± 2 nm). Results based on nitrogen adsorption/desorption isotherms, thermogravimetric analysis (TGA), Fourier transform infrared (FTIR), and UV–vis analysis confirmed functionalization on MSN with targeting moiety, chalcone, and chelating agent, DTPA. A red shift to 30 nm and a 4-fold increase in emission intensity of the fluorescent spectrum of the nanomaterial upon treatment with Aβ42 aggregate, indicated interaction between Aβ42 aggregate and MSN-DTPA-Chal. The MTT assay indicated >90% cell viability in PC12 and HEK-293 cell lines after coincubation with nanoparticles at 48 h. Radiolabeled complex of MSN-DTPA-Chal with radioisotope, 99mTc, had >99% radiochemical purity. In vivo single photon emission computed tomography (SPECT) imaging on healthy rabbits demonstrated the effective penetration of MSN-DTPA-Chal into the brain. Further, a nonsurgical rmTBI model overexpressing Aβ42 plaques was developed, and the formation of Aβ42 plaques was confirmed using histological analysis, ThS staining, and immunohistochemistry. The biodistribution studies revealed significant brain uptake (4.42 ± 0.72% ID/g) of 99mTc-MSN-DTPA-Chal in Aβ42 plaques overexpressed TBI mice after 2 h with slow washout (3.94 ± 0.13% ID/g at 4 h), compared to control mice (0.25 ± 0.12% ID/g at 4 h), possibly due to binding of nanoparticles with Aβ42 aggregates. Curcumin-loaded nanoparticles had a biphasic sustained release pattern, demonstrating the efficacy of the developed system in delivering drugs in a controlled manner.