Brain-derived neurotrophic factor (BDNF) is identified as a potent neuroprotective and neuroregenerative agent for many neurological diseases. Regrettably, its delivery to the brain is hampered by poor serum stability and rapid brain clearance. Here, a novel nanoformulation is reported composed of a bio-compatible polymer, poly(ethylene glycol)--poly(L-glutamic acid) (PEG-PLE), that hosts the BDNF molecule in a nanoscale complex, termed here Nano-BDNF. Upon simple mixture, Nano-BDNF spontaneously forms uniform spherical particles with a core-shell structure. Molecular dynamics simulations suggest that binding between BDNF and PEG-PLE is mediated through electrostatic coupling as well as transient hydrogen bonding. The formation of Nano-BDNF complex stabilizes BDNF and protects it from nonspecific binding with common proteins in the body fluid, while allowing it to associate with its receptors. Following intranasal administration, the nanoformulation improves BDNF delivery throughout the brain and displays a more preferable regional distribution pattern than the native protein. Furthermore, intranasally delivered Nano-BDNF results in superior neuroprotective effects in the mouse brain with lipopolysaccharides-induced inflammation, indicating promise for further evaluation of this agent for the therapy of neurologic diseases.

The photoluminescence of lanthanide ions inside fullerenes is usually very weak due to the quenching effect of the fullerene cage. In the case of Er@C 82 , the near-infrared emission from the Er 3+ ion is completely quenched by the C 82 fullerene cage. It remains challenging to turn on the photoluminescence of Er@C 82 and other monometallofullerenes. In this work, we adopt a covalent modification strategy to alter the electronic structure of the fullerene cage for sensitizing the near-infrared emission of Er 3+ ions in metallofullerenes Er@C 2n (2n = 72, 76, and 82). After covalent modification with trifluoromethyl, phenyl, or dichlorophenyl groups, the erbium metallofullerenes exhibit photoluminescence at 1.5 μm, which is the characteristic emission of the Er 3+ ion. Particularly, the otherwise nonfluorescent metallofullerene Er@C 82 is transformed into fluorescent derivatives by using this strategy. The photoluminescence from the Er 3+ ion is ascribed to energy transfer from the fullerene cage to the Er 3+ ion. According to theoretical calculations, the sensitization of the Er 3+ ion by the fullerene cage is associated with the large HOMO−LUMO gap and the closed-shell electronic structure of the metallofullerene derivatives. This work provides useful guidance for the design and synthesis of new fluorescent metallofullerenes.

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Background Low levels of brain-derived neurotrophic factor (BDNF) are linked to delayed neurological recovery, depression, and cognitive impairment following stroke. Supplementation with BDNF reverses these effects. Unfortunately, systemically administered BDNF in its native form has minimal therapeutic value due to its poor blood brain barrier permeability and short serum half-life. In this study, a novel nano-particle polyion complex formulation of BDNF (nano-BDNF) was administered to mice after experimental ischemic stroke. Methods Male C57BL/6J (8–10 weeks) mice were randomly assigned to receive nano-BDNF, native-BDNF, or saline treatment after being subjected to 60 minutes of reversible middle cerebral artery occlusion (MCAo). Mice received the first dose at 3 (early treatment), 6 (intermediate treatment), or 12 hours (delayed treatment) following stroke onset; a second dose was given in all cohorts at 24 hours after stroke onset. Post-stroke outcome was evaluated by behavioral, histological, and molecular analysis for 15 days after stroke. Results Early and intermediate nano-BDNF treatment led to a significant reduction in cerebral tissue loss. Delayed treatment led to improved memory/cognition, reduced post-stroke depressive phenotypes, and maintained myelin basic protein and brain BDNF levels, but had no effect on tissue atrophy. Conclusions The results indicate that administration of a novel nano-particle formulation of BDNF leads to both neuroprotective and neuro-restorative effects after stroke.

The design of molecular rotors that can rotate in ultrahigh speeds is important for the development of artificial molecular machines. Based on theoretical calculations, we demonstrate that two kinds of...

Copper/zinc superoxide dismutase (CuZnSOD; SOD1) is widely considered as a potential therapeutic candidate for pathologies involving oxidative stress, but its application has been greatly hindered by delivery issues. In our previous study, nano-formulated SOD1 (cl-nanozyme) was shown to decrease infarct volume and improve sensorimotor functions after single intravenous (IV) injection in a rat middle cerebral artery occlusion (MCAO) model of ischemia/reperfusion (I/R) injury. However, it remained unclear how cl-nanozyme was able to deliver SOD1 to the brain and exert therapeutic efficacy. Present study aims to answer this question by exploring micro-distribution pattern of cl-nanozyme in the rat brain after stroke. Immunohistochemistry studies demonstrated cl-nanozyme co-localization with fibrin along damaged arteries and capillaries in the ischemic hemisphere. We further found that cl-nanozyme can be cross-linked into thrombi formed after I/R injury in the brain, and this effect is independent of animal species (rat/mouse) used for modeling I/R injury. This work is also the first report reinforcing therapeutic potential of cl-nanozyme in a well-characterized mouse MCAO model of I/R injury.

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