Continuous synthesis of PEGylated MIL-101(Cr) nanoparticles for neuroprotection

The application of metal organic frameworks (MOFs) in targeted drug delivery for ischemic stroke therapy has emerged as a hot issue recently. Although significant progress has been made in immobilizing neuroprotective agents on MOFs, environmentally friendly large-scale preparation of nano-drug-loaded MOFs with controlled size, morphology, purity and therapeutic effect remains challenging. PEGylation of MIL-101(Cr) nanoparticles with dual ligands that have the 2,2-dimethylthiazolidine (DMTD) structure was developed in this work to mitigate nervous system injury induced by ischemia/reperfusion (IR) during a stroke. A green ultrasound-assisted continuous-flow system was established for efficient production of the versatile MOF nanoparticles. Unified nanoparticles (diameter: ∼250-350 nm) were obtained with both high quality and high space-time yield (5664 kg m^-3 d^-1). The MOF exhibited protective activity in SH-SY5Y cells against oxygen and glucose deprivation and H₂O₂ insults, and prevented reactive oxygen species accumulation. The cellular uptake of the PEGylated MOFs by brain capillary endothelial cells was investigated, showing targeting capability in vitro, which proposes the biomaterial as a promising therapeutic candidate for reducing IR-induced nervous system injury.