Qiushi Academy for Advanced Studies, Zhejiang University , Hangzhou 310027, China.
ACS Nano. 2015 Jan 27;9(1):799-808. doi: 10.1021/nn5063276. Epub 2015 Jan 15.
Heat-lability is a key roadblock that strangles the widespread applications of many biological products. In nature, archaeal and extremophilic organisms utilize amorphous silica as a protective biomineral and exhibit considerable thermal tolerance. Here we present a bioinspired approach to generate thermostable virus by introducing an artificial hydrated silica exterior on individual virion. Similar to thermophiles, silicified viruses can survive longer at high temperature than their wild-type relatives. Virus inactivation assays showed that silica hydration exterior of the modified virus effectively prolonged infectivity of viruses by ∼ 10-fold at room temperature, achieving a similar result as that obtained by storing native ones at 4 °C. Mechanistic studies indicate that amorphous silica nanoclusters stabilize the inner virion structure by forming a layer that restricts molecular mobility, acting as physiochemical nanoanchors. Notably, we further evaluate the potential application of this biomimetic strategy in stabilizing clinically approved vaccine, and the silicified polio vaccine that can retain 90% potency after the storage at room temperature for 35 days was generated by this biosilicification approach and validated with in vivo experiments. This approach not only biomimetically connects inorganic material and living virus but also provides an innovative resolution to improve the thermal stability of biological agents using nanomaterials.
热不稳定性是许多生物制品广泛应用的关键障碍。在自然界中,古菌和极端微生物利用无定形二氧化硅作为保护性生物矿化物质,并表现出相当大的热耐受性。在这里,我们提出了一种仿生方法,通过在单个病毒粒子上引入人工水合二氧化硅外壳来产生热稳定的病毒。与嗜热菌类似,硅化病毒在高温下的存活时间比它们的野生型亲缘病毒更长。病毒失活实验表明,修饰病毒的硅水合外壳可使病毒在室温下的感染力有效延长约 10 倍,达到与在 4°C 下储存天然病毒相似的效果。机制研究表明,无定形硅纳米簇通过形成限制分子流动性的层来稳定内部病毒结构,充当物理化学纳米锚点。值得注意的是,我们进一步评估了这种仿生策略在稳定临床批准疫苗方面的潜在应用,通过这种生物硅化方法生成了硅化脊髓灰质炎疫苗,在室温下储存 35 天后仍保持 90%的效力,并通过体内实验进行了验证。这种方法不仅仿生地连接了无机材料和活病毒,而且还为使用纳米材料提高生物制剂的热稳定性提供了一种创新的解决方案。