The in vivo fates of plant viral nanoparticles camouflaged using self-proteins: overcoming immune recognition.,Journal of Materials Chemistry B

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The in vivo fates of plant viral nanoparticles camouflaged using self-proteins: overcoming immune recognition.
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2018-02-27 00:00:00 , DOI: 10.1039/c7tb03106h
N M Gulati _{1,

2} , A S Pitek ₃ , A E Czapar ₃ , P L Stewart _{1,

2} , N F Steinmetz _{3,

4,

5,

6,

7}

Affiliation

Nanoparticles offer a promising avenue for the targeted delivery of therapies. To slow clearance, nanoparticles are frequently stealth-coated to prevent opsonization and immune recognition. Serum albumin (SA) has been used as a bio-inspired stealth coating. To develop this shielding strategy for clinical applications, it is critical to understand the interactions between the immune system and SA-camouflaged nanoparticles. This work investigates the in vivo processing of SA-coated nanoparticles using tobacco mosaic virus (TMV) as a model system. In comparing four different SA-formulations, the particles with high SA coverage conjugated to TMV via a short linker performed the best at preventing antibody recognition. All formulations led to similar levels of TMV-specific antibodies after repeat administration in mice; importantly though, SA-specific antibodies were not detected and the TMV-specific antibodies were unable to recognize shielded SA-coated TMV. Upon uptake in macrophages, the shielding agent and nanoparticle separate, where TMV trafficked to the lysosome and SA appears to recycle. The distinct intracellular fates of the TMV carrier and SA shielding agent explain why anti-TMV but not SA-specific antibodies are generated. This work characterizes the outcomes of SA-camouflaged TMV after immune recognition, and highlights the effectiveness of SA as a nanoparticle shielding agent.

中文翻译：

使用自身蛋白伪装的植物病毒纳米粒子的体内命运：克服免疫识别。

纳米颗粒为靶向治疗提供了一种有前景的途径。为了减缓清除速度，纳米颗粒经常被隐形涂层以防止调理作用和免疫识别。血清白蛋白（SA）已被用作仿生隐形涂层。为了开发这种临床应用的屏蔽策略，了解免疫系统和 SA 伪装纳米颗粒之间的相互作用至关重要。这项工作使用烟草花叶病毒 (TMV) 作为模型系统，研究了 SA 涂层纳米颗粒的体内加工。在比较四种不同的 SA 制剂时，通过短接头与 TMV 缀合的具有高 SA 覆盖率的颗粒在防止抗体识别方面表现最好。在小鼠体内重复给药后，所有制剂均产生相似水平的 TMV 特异性抗体；但重要的是，没有检测到 SA 特异性抗体，并且 TMV 特异性抗体无法识别屏蔽的 SA 包被的 TMV。巨噬细胞吸收后，屏蔽剂和纳米颗粒分离，其中 TMV 被运输到溶酶体，而 SA 似乎会循环利用。 TMV 载体和 SA 屏蔽剂的不同细胞内命运解释了为什么产生抗 TMV 而不是 SA 特异性抗体。这项工作描述了 SA 伪装的 TMV 在免疫识别后的结果，并强调了 SA 作为纳米粒子屏蔽剂的有效性。

更新日期：2018-02-27

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