Kos Spela, Vanvarenberg Kevin, Dolinsek Tanja, Cemazar Maja, Jelenc Jure, Préat Véronique, Sersa Gregor, Vandermeulen Gaëlle
Institute of Oncology Ljubljana, Department of Experimental Oncology, Zaloska 2, SI-1000 Ljubljana, Slovenia.
Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue E. Mounier, 73 bte B 1.73.12, 1200 Brussels, Belgium.
Bioelectrochemistry. 2017 Apr;114:33-41. doi: 10.1016/j.bioelechem.2016.12.002. Epub 2016 Dec 10.
Skin is an attractive target for gene electrotransfer due to its easy accessibility and its interesting immune properties. Since electrodes are often invasive and frequently induce discomfort during pulse application, there is a fundamental need for non-invasive electrodes for skin delivery. We developed circular pin non-invasive multi-electrode array (MEA), suitable for different clinical applications. MEA was first employed to deliver a luciferase reporter gene. Then, it was used to deliver a DNA vaccine coding for ovalbumin or a plasmid encoding hCAP-18/LL-37 for promoting wound healing. The results demonstrated a strong gene expression and an efficient delivery of both, DNA vaccine and wound healing agent, dependent on the pulses applied. The use of MEA to deliver the ovalbumin plasmid demonstrated a strong immune response, as evidenced by the presence of antibodies in sera, the IFN-gamma response and the delayed tumor growth when the mice were subsequently challenged with B16-OVA cells. The delivery of a plasmid encoding hCAP-18/LL-37 significantly accelerated wound closure. The easy applicability and non-invasiveness of MEA make it suitable for various clinical applications that require gene electrotransfer to skin. Specifically, by adapting electric pulses to the expected action of a transgene, non-invasive MEA can be employed either for vaccination or for wound healing.
由于皮肤易于接近且具有有趣的免疫特性，因此它是基因电转移的一个有吸引力的靶点。由于电极通常具有侵入性，并且在施加脉冲期间经常会引起不适，所以根本需要用于皮肤给药的非侵入性电极。我们开发了适用于不同临床应用的圆形针非侵入性多电极阵列（MEA）。MEA首先用于递送荧光素酶报告基因。然后，它被用于递送编码卵清蛋白的DNA疫苗或编码hCAP-18/LL-37以促进伤口愈合的质粒。结果表明，取决于所施加的脉冲，基因表达强烈，并且DNA疫苗和伤口愈合剂的递送均有效。使用MEA递送卵清蛋白质粒显示出强烈的免疫反应，血清中存在抗体、IFN-γ反应以及当小鼠随后用B16-OVA细胞攻击时肿瘤生长延迟证明了这一点。递送编码hCAP-18/LL-37的质粒显著加速了伤口闭合。MEA的易于应用和非侵入性使其适用于各种需要基因电转移至皮肤的临床应用。具体而言，通过使电脉冲适应转基因的预期作用，非侵入性MEA可用于疫苗接种或伤口愈合。
