The blood-brain barrier is the major obstacle that prevents diagnostic and therapeutic drugs being delivered to the central nervous systems in order to exert their effects. Specific ligand-receptor binding mediated endocytosis is one of the possible strategies to cross this barrier. A 30-amino-acid peptide (leptin30) derived from an endogenic hormone-leptin is exploited as brain-targeting ligand as it is reported to possess the same brain accumulation efficiency after intravenous injection. Dendrigraft poly-l-lysine (DGL) is used as non-viral gene vector in this study. DGL-PEG-Leptin30 was complexed with plasmid DNA yielding nanoparticles (NPs). The cellular uptake characteristic and mechanism were explored in brain capillary endothelial cells (BCECs) which express leptin receptors. Furthermore, brain parenchyma microglia cells such as BV-2 cells expressing leptin receptors could promote ligand-receptor mediated endocytosis leading to enhanced gene transfection ability of DGL-PEG-Leptin30/DNA NPs. The targeted NPs were proved to be transported across in vitro BBB model effectively and accumulate more in brains after i.v. resulting in a relatively high gene transfection efficiency both in vitro and in vivo. Besides, the NPs showed low cytotoxicity after in vitro transfection. Thus, DGL-PEG-Leptin30 provides a safe and noninvasive approach for the delivery of gene across the blood-brain barrier.
Vibrational optical activity (VOA) spectra, such as vibrational circular
dichroism (VCD) and Raman optical activity (ROA) spectra, of aliphatic amino
acids are simulated using density functional theory (DFT) methods in both gas
phase (neutral form) and solution (zwitterionic form), together with th...
A nonlinear Tracking-Differentiator is one-input-two-output system that can
generate smooth approximation of measured signals and get the derivatives of
the signals. The nonlinear tracking-Differentiator is explored to denoise and
generate the derivatives of the walks of the 3-periodicity of DNA se...
: A total of 10,669 patients were included with a 4.5% readmission rate. The study cohort was on average 49.5 years of age, 32.2% were obese, and 15.2% were smokers. The majority of patients were female (81.7%). Cases were predominantly outpatient procedures (65.6%). The most commonly performed proce...
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