ROS-responsive biomimetic nanosystem camouflaged by hybrid membranes of platelet-exosomes engineered with neuronal targeting peptide for TBI therapy.

Recovery and survival following traumatic brain injury (TBI) depends on optimal amelioration of secondary injuries at lesion site. Delivering mitochondria-protecting drugs to neurons may revive damaged neurons at sites secondarily traumatized by TBI. Pioglitazone (PGZ) is a promising candidate for TBI treatment, limited by its low brain accumulation and poor targetability to neurons. Herein, we report a ROS-responsive nanosystem, camouflaged by hybrid membranes of platelets and engineered extracellular vesicles (EVs) (C3-EPm-|TKNPs|), that can be used for targeted delivery of PGZ for TBI therapy. Inspired by intrinsic ability of macrophages for inflammatory chemotaxis, engineered M2-like macrophage-derived EVs were constructed by fusing C3 peptide to EVs membrane integrator protein, Lamp2b, to confer them with ability to target neurons in inflamed lesions. Platelets provided hybridized EPm with capabilities to target hemorrhagic area caused by trauma via surface proteins. Consequently, C3-EPm-|PGZ-TKNPs| were orientedly delivered to neurons located in the traumatized hemisphere after intravenous administration, and triggered the release of PGZ from TKNPs via oxidative stress. The current work demonstrate that C3-EPm-|TKNPs| can effectively deliver PGZ to alleviate mitochondrial damage via mitoNEET for neuroprotection, further reversing behavioral deficits in TBI mice. Our findings provide proof-of-concept evidence of C3-EPm-|TKNPs|-derived nanodrugs as potential clinical approaches against neuroinflammation-related intracranial diseases.

DFT characterization of a new possible two-dimensional BN allotrope with a biphenylene network structure.

The pioneering work on the newly experimentally synthesized biphenylene network C has triggered a worldwide tide of research on its family material counterparts. In this study, a biphenylene network BN structure was theoretically characterized by density functional theory (DFT) calculations. Initially, the structure's mechanical and thermal stabilities were evaluated. There were no imaginary frequencies in the phonon dispersion curve, indicating that the structure was mechanically stable. Additionally, the energy barrier for forming a biphenylene network BN structure from perfect pristine 2D h-BN is substantially less than that for forming a biphenylene network C from a perfect graphene sheet, as can be explained from the greater structure distortion in the biphenylene network BN with lower bond stress which thus caused lower energy. The electronic band structure and detailed projected density of states analysis indicated that the biphenylene network BN is a semiconductor with the valence band maximum (VBM) and the conduction band minimum (CBM) states from the pz orbitals of N and B atoms with sp2 hybridization. Finally, a bilayer structure was also proposed. Our obtained results provide more insights into two-dimensional biphenylene network BN based structures and those family materials which could be widely used in relevant nanoelectronic devices.