Advanced search×

A leptin derived 30-amino-acid peptide modified pegylated poly-l-lysine dendrigraft for brain targeted gene delivery

Yang Liu, Jianfeng Li, Kun Shao, Rongqin Huang, Liya Ye, Jinning Lou, and Chen Jiang

Biomaterials 31(19):12 (2010) PMID 20382424

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.

Copyright © 2010 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.biomaterials.2010.03.011
Version: za2963e q8za8 q8zbc q8zc1 q8zd3 q8zec q8zf3 q8zga

Similar articles you may find interesting…

  1. A study of aliphatic amino acids using simulated vibrational circular dichroism and Raman optical activity spectra
    Aravindhan Ganesan, Michael J Brunger, and Feng Wang

    arXiv:1305.5290 [physics.chem-ph] 22 May 2013

    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...
    View PDF
  2. Denoising the 3-Base Periodicity Walks of DNA Sequences in Gene Finding
    Changchuan Yin, Dongchul Yoo, and Stephen S-T Yau

    arXiv:1305.5524 [cs.CE] 23 May 2013

    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...
    View PDF
  3. Factors associated with readmission following plastic surgery- a review of 10,669 procedures from 2011 American College of Surgeons Nation S...
    John P Fischer, Ari Wes, and Stephen J Kovach

    Plast Reconstr Surg (2013) PMID 23676965

    : 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...