Naszályi Nagy Livia, Dhaene Evert, Van Zele Matthias, Mihály Judith, Klébert Szilvia, Varga Zoltán, Kövér Katalin E, De Buysser Klaartje, Van Driessche Isabel, Martins José C, Fehér Krisztina
NMR and Structure Analysis Research Group, Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281 S4, B-9000 Ghent, Belgium.
Sol-Gel Centre for Research on Inorganic Powders and Thin Films Synthesis, Department of Chemistry, Ghent University, Krijgslaan 281 S3, B-9000 Ghent, Belgium.
Nanomaterials (Basel). 2021 Aug 25;11(9):2166. doi: 10.3390/nano11092166.
The development of delivery systems for the immobilization of nucleic acid cargo molecules is of prime importance due to the need for safe administration of DNA or RNA type of antigens and adjuvants in vaccines. Nanoparticles (NP) in the size range of 20-200 nm have attractive properties as vaccine carriers because they achieve passive targeting of immune cells and can enhance the immune response of a weakly immunogenic antigen via their size. We prepared high capacity 50 nm diameter silica@zirconia NPs with monoclinic/cubic zirconia shell by a green, cheap and up-scalable sol-gel method. We studied the behavior of the particles upon water dialysis and found that the ageing of the zirconia shell is a major determinant of the colloidal stability after transfer into the water due to physisorption of the zirconia starting material on the surface. We determined the optimum conditions for adsorption of DNA building blocks, deoxynucleoside monophosphates (dNMP), the colloidal stability of the resulting NPs and its time dependence. The ligand adsorption was favored by acidic pH, while colloidal stability required neutral-alkaline pH; thus, the optimal pH for the preparation of nucleic acid-modified particles is between 7.0-7.5. The developed silica@zirconia NPs bind as high as 207 mg dNMPs on 1 g of nanocarrier at neutral-physiological pH while maintaining good colloidal stability. We studied the influence of biological buffers and found that while phosphate buffers decrease the loading dramatically, other commonly used buffers, such as HEPES, are compatible with the nanoplatform. We propose the prepared silica@zirconia NPs as promising carriers for nucleic acid-type drug cargos.
由于在疫苗中安全施用DNA或RNA类型的抗原和佐剂的需求，用于固定核酸货物分子的递送系统的开发至关重要。尺寸范围在20-200nm的纳米颗粒（NP）作为疫苗载体具有吸引人的特性，因为它们能够实现对免疫细胞的被动靶向，并且可以通过其尺寸增强弱免疫原性抗原的免疫反应。我们通过一种绿色、廉价且可扩大规模的溶胶-凝胶法制备了具有单斜/立方氧化锆壳的直径为50nm的高容量二氧化硅@氧化锆NP。我们研究了颗粒在水透析后的行为，发现氧化锆壳的老化是转移到水中后胶体稳定性的主要决定因素，这是由于氧化锆起始材料在表面的物理吸附。我们确定了DNA构建块、脱氧核苷单磷酸（dNMP）吸附的最佳条件、所得NP的胶体稳定性及其时间依赖性。配体吸附在酸性pH下更有利，而胶体稳定性需要中性-碱性pH；因此，制备核酸修饰颗粒的最佳pH在7.0-7.5之间。所开发的二氧化硅@氧化锆NP在中性生理pH下，每克纳米载体可结合高达207mg的dNMP，同时保持良好的胶体稳定性。我们研究了生物缓冲液的影响，发现虽然磷酸盐缓冲液会显著降低负载量，但其他常用缓冲液，如HEPES，与纳米平台兼容。我们提出所制备的二氧化硅@氧化锆NP作为核酸类药物货物的有前景的载体。
