Solid Lipid Nanoparticle Carrier Platform Containing Synthetic TLR4 Agonist Mediates Non-Viral DNA Vaccine Delivery.
Solid Lipid Nanoparticle Carrier Platform Containing Synthetic TLR4 Agonist Mediates Non-Viral DNA Vaccine Delivery.
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DOI：
10.3390/vaccines8030551
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发表时间：
2020-09-21
期刊：
影响因子：
7.8
通讯作者：
Smooker PM
中科院分区：
文献类型：
--
作者：
Francis JE;Skakic I;Dekiwadia C;Shukla R;Taki AC;Walduck A;Smooker PM
人们对更好的递送系统的需求不断增长，以提高 DNA 疫苗的稳定性和功效。在此，我们报告了一种非病毒 DNA 疫苗递送系统的合成，该系统使用新型佐剂固体脂质纳米颗粒 (SLN-A) 平台作为编码来自幽门螺杆菌的尿素酶 α (UreA) 抗原的 DNA 疫苗候选物的载体。采用改进的溶剂乳化法合成了含有单磷酰脂质 A（佐剂）的阳离子 SLN-A 颗粒，并研究了其形态、zeta 电位和体外转染能力。发现颗粒与质粒 DNA 结合形成脂质复合物，并通过电子显微镜、动态光散射和荧光显微镜对其进行了表征。细胞摄取研究证实了颗粒在 3 小时内被摄取，并在内体室内定位于细胞内。体外研究进一步证实了 SLN-A 颗粒能够刺激人巨噬细胞样东北医院儿科-1 (THP-1) 细胞中促炎细胞因子肿瘤坏死因子 α (TNF-α) 的表达。脂质复合物被发现具有生物相容性，并且可以有效地转染到小鼠免疫细胞中以表达重组幽门螺杆菌抗原脲酶A，这证明了它们作为DNA疫苗递送系统的潜力。
There is a growing demand for better delivery systems to improve the stability and efficacy of DNA vaccines. Here we report the synthesis of a non-viral DNA vaccine delivery system using a novel adjuvanted solid lipid nanoparticle (SLN-A) platform as a carrier for a DNA vaccine candidate encoding the Urease alpha (UreA) antigen from Helicobacter pylori. Cationic SLN-A particles containing monophosphoryl lipid A (adjuvant) were synthesised by a modified solvent-emulsification method and were investigated for their morphology, zeta potential and in vitro transfection capacity. Particles were found to bind plasmid DNA to form lipoplexes, which were characterised by electron microscopy, dynamic light scattering and fluorescence microscopy. Cellular uptake studies confirmed particle uptake within 3 h, and intracellular localisation within endosomal compartments. In vitro studies further confirmed the ability of SLN-A particles to stimulate expression of pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) in human macrophage-like Tohoku Hospital Pediatrics-1 (THP-1) cells. Lipoplexes were found to be biocompatible and could be efficiently transfected in murine immune cells for expression of recombinant H. pylori antigen Urease A, demonstrating their potential as a DNA vaccine delivery system.
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DOI：
10.1615/critrevtherdrugcarriersyst.v26.i6.10
发表时间：
2009
影响因子：
2.7
作者：
Puri A;Loomis K;Smith B;Lee JH;Yavlovich A;Heldman E;Blumenthal R
通讯作者：
Blumenthal R
影响因子：
6
作者：
Ko EJ;Lee YT;Lee Y;Kim KH;Kang SM
通讯作者：
Kang SM
影响因子：
10.8
作者：
Thomann-Harwood, L. J.;Kaeuper, P.;McCullough, K. C.
通讯作者：
McCullough, K. C.
影响因子：
13.3
作者：
Poddar, Arpita;Conesa, Jose J.;Shukla, Ravi
通讯作者：
Shukla, Ravi
影响因子：
2.5
作者：
Penumarthi, Alekhya;Parashar, Deepti;Smooker, Peter M.
通讯作者：
Smooker, Peter M.