pH Responsive Poly(Amino Acid) Nanoparticles as Potent Carrier Adjuvants for Enhancing Cellular Immunity,Macromolecular Bioscience

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pH Responsive Poly(Amino Acid) Nanoparticles as Potent Carrier Adjuvants for Enhancing Cellular Immunity
Macromolecular Bioscience ( IF 4.4 ) Pub Date : 2023-03-23 , DOI: 10.1002/mabi.202200520
Jiarui Zhang ₁ , Yian Liu ₁ , Lintao Bai ₁ , Gan Gao ₁ , Yuxuan Li ₁ , Heyun Shen ₁

Affiliation

Adjuvants are widely used in vaccine to improve the protection or treatment efficacy. However, so far they inevitably produce side effects and are hard to induce cellular immunity in practical application. Herein, two kinds of amphiphilic poly(glutamic acid) nanoparticles (α-PGA-F and γ-PGA-F NPs) as nanocarrier adjuvants are fabricated to induce an effective cellular immune response. Amphiphilic PGA are synthesized by grafting phenylalanine ethyl ester to form biodegradable self-assembly nanoadjuvants in a water solution. The model antigen, chicken ovalbumin (OVA), can be loaded into PGA-F NPs (OVA@PGA-F NPs) with the high loading ratio >12%. Moreover, compared with γ-PGA-F NPs, the acidic environment can induce the α-helical secondary structure of α-PGA NPs, promoting membrane fusion and more fast antigen lysosomal escape. Hence, the antigen presenting cells treated with OVA@α-PGA-F NPs show higher secretion of inflammatory cytokines, and higher expression of major biological histocompatibility complex class I and CD80 than those of OVA@γ-PGA-F NPs. Overall, this work indicates that pH responsive α-PGA-F NPs as a carrier adjuvant can effectively improve the ability of cellular immune responses, leading to it being a potent candidate for vaccine applications.

中文翻译：

pH 响应聚（氨基酸）纳米颗粒作为增强细胞免疫力的有效载体佐剂

佐剂广泛用于疫苗中以提高保护或治疗效果。然而，迄今为止，它们不可避免地会产生副作用，并且在实际应用中难以诱导细胞免疫。在此，制备了两种两亲性聚（谷氨酸）纳米粒子（α -PGA-F 和γ -PGA-F NPs）作为纳米载体佐剂以诱导有效的细胞免疫反应。通过接枝苯丙氨酸乙酯在水溶液中形成可生物降解的自组装纳米佐剂来合成两亲性PGA。模型抗原鸡卵清蛋白 (OVA) 可以加载到 PGA-F NPs (OVA@PGA-F NPs) 中，加载率 >12%。此外，与γ -PGA-F NPs相比，酸性环境可以诱导α-α -PGA NPs的螺旋二级结构，促进膜融合和更快的抗原溶酶体逃逸。因此，与 OVA@ γ -PGA-F NPs 相比，用 OVA@ α -PGA-F NPs处理的抗原呈递细胞表现出更高的炎性细胞因子分泌，以及主要生物组织相容性复合物 I 类和 CD80 的更高表达。总的来说，这项工作表明 pH 响应性α -PGA-F NPs 作为载体佐剂可以有效提高细胞免疫反应的能力，使其成为疫苗应用的有力候选者。

更新日期：2023-03-23

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