Paradox of PEGylation in fabricating hybrid nanoparticle-based nicotine vaccines.
Paradox of PEGylation in fabricating hybrid nanoparticle-based nicotine vaccines.
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DOI：
10.1016/j.biomaterials.2018.08.015
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发表时间：
2018-11
期刊：
影响因子：
14
通讯作者：
Zhang C
中科院分区：
文献类型：
--
作者：
Hu Y;Zhao Z;Harmon T;Pentel PR;Ehrich M;Zhang C
聚乙二醇（PEG）长期以来一直用于基于纳米颗粒的药物或疫苗递送平台。本研究将纳米尼古丁疫苗（NanoNicVac）进行不同程度的PEG化，考察PEG对疫苗免疫效力的影响。组装具有不同聚乙二醇化程度（2.5%-30%）的混合纳米颗粒。发现30%PEG化导致折衷的核-壳结构的混合纳米颗粒。较高浓度的PEG也导致树突状细胞对混合纳米颗粒的细胞摄取较慢。然而，增加PEG的量可以有效地减少纳米粒子在储存过程中的聚集，提高杂化纳米粒子的稳定性。随后，通过将尼古丁半抗原缀合至不同聚乙二醇化的混合纳米颗粒来合成尼古丁疫苗。在体外和体内研究中，发现具有20% PEG化的尼古丁疫苗（NanoNicVac 20.0）比具有较低PEG化的疫苗显著更稳定。此外，NanoNicVac 20.0在小鼠中诱导的抗尼古丁抗体滴度（3.7 ± 0.6 × 104）显著高于PEG浓度较低的其他NanoNicVac。在随后的药代动力学研究中，在用NanoNicVac 20.0免疫的小鼠中检测到最低脑尼古丁浓度34 ± 11 ng/g。此外，在用NanoNicVac免疫的小鼠中未观察到明显的不良事件。总之，20%聚乙二醇化赋予NanoNicVac在小鼠中具有理想的安全性、最高的稳定性和最佳的免疫功效。
Polyethylene glycol (PEG) has long been used in the nanoparticle-based drug or vaccine delivery platforms. In this study nano-nicotine vaccines (NanoNicVac) were PEGylated to different degrees to investigate the impact of PEG on the immunological efficacy of the vaccine. Hybrid nanoparticles with various degrees of PEGylation (2.5%−30%) were assembled. It was found that 30% PEGylation resulted in a hybrid nanoparticle of a compromised core-shell structure. A higher concentration of PEG also led to a slower cellular uptake of hybrid nanoparticles by dendritic cells. However, increasing the quantity of the PEG could effectively reduce nanoparticle aggregation during storage and improve the stability of the hybrid nanoparticles. Subsequently, nicotine vaccines were synthesized by conjugating nicotine haptens to the differently PEGylated hybrid nanoparticles. In both in vitro and in vivo studies, it was found that a nicotine vaccine with 20% PEGylation (NanoNicVac 20.0) was significantly more stable than the vaccines with lower PEGylation. In addition, NanoNicVac 20.0 induced a significantly higher anti-nicotine antibody titer of 3.7±0.6×104 in mice than the other NanoNicVacs with lower concentrations of PEG. In a subsequent pharmacokinetic study, the lowest brain nicotine concentration of 34±11 ng/g was detected in mice that were immunized with NanoNicVac 20.0. In addition, no apparent adverse events were observed in mice immunized with NanoNicVac. In summary, 20% PEGylation confers NanoNicVac with desirable safety, the highest stability, and the best immunological efficacy in mice.
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影响因子：
5
作者：
Makadia HK;Siegel SJ
通讯作者：
Siegel SJ
DOI：
10.1016/b978-0-12-420118-7.00014-7
发表时间：
2014-01-01
期刊：
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影响因子：
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作者：
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通讯作者：
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作者：
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作者：
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通讯作者：
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影响因子：
7.3
作者：
Avalos AM;Ploegh HL
通讯作者：
Ploegh HL