Biodegradable nanoparticles composed of enantiomeric poly(γ-glutamicacid)-graft-poly(lactide) copolymers as vaccine carriers for dominant induction of cellular immunity
Biodegradable nanoparticles composed of enantiomeric poly(γ-glutamicacid)-graft-poly(lactide) copolymers as vaccine carriers for dominant induction of cellular immunity
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由对映体聚（γ-谷氨酸）-接枝-聚（丙交酯）共聚物组成的可生物降解纳米粒子作为疫苗载体，用于显着诱导细胞免疫
DOI：
10.1039/c3bm60279f
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Mitsuru Akashi
中科院分区：
文献类型：
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作者：
Takami Akagi;Ye Zhu;Fumiaki Shima;Mitsuru Akashi
在所需位点具有受控降解的颗粒材料的设计在药物/疫苗/基因递送系统的应用中是重要的。两亲性生物可降解聚合物纳米颗粒是有前途的疫苗递送载体，因为它们能够稳定地维持抗原，提供定制的释放动力学，有效地靶向，并用作佐剂。本文报道了由聚γ-谷氨酸-聚丙交酯（γ-PGA-PLA）共聚物组成的立体复合物纳米粒（SC NPs）是一种优良的蛋白质疫苗载体，可将抗原蛋白递送至树突状细胞（DCs），并引发有效的免疫应答。我们制备了卵清蛋白（OVA）包封的γ-PGA-PLA SC NP（OVA-SC NP）和异构体NP。这些NP被DC有效地摄取，并且还影响包封的OVA的细胞内降解。与游离OVA和相应的异构体NP相比，包封到SC NP中的OVA的降解减弱。有趣的是，用OVA-SC NP免疫主要诱导抗原特异性细胞免疫。由PLA组成的内部NPs的晶体结构对NPs的降解曲线和包封抗原的释放/降解行为以及因此免疫诱导的效率具有显著影响。我们的研究结果表明，γ-PGA-PLA SC NP适用于用于诱导细胞免疫的基于蛋白质的疫苗，例如用于感染性疾病、癌症、过敏和自身免疫性疾病。
The design of particulate materials with controlled degradation at desired sites is important in applications for drug/vaccine/gene delivery systems. Amphiphilic biodegradable polymeric nanoparticles are promising vaccine delivery carriers due to their ability to stably maintain antigens, provide tailored release kinetics, effectively target, and function as adjuvants. In this study, we report that stereocomplex nanoparticles (SC NPs) composed of enantiomeric poly(γ-glutamic acid)-graft-poly(lactide) (γ-PGA–PLA) copolymers are excellent protein delivery carriers for vaccines that can deliver antigenic proteins to dendritic cells (DCs) and elicit potent immune responses. We prepared ovalbumin (OVA)-encapsulated γ-PGA–PLA SC NPs (OVA-SC NPs) and isomer NPs. These NPs were efficiently taken up by DCs and also affected the intracellular degradation of the encapsulated OVA. The degradation of OVA encapsulated into the SC NPs was attenuated as compared to free OVA and the corresponding isomer NPs. Interestingly, immunization with OVA-SC NPs predominantly induced antigen-specific cellular immunity. The crystalline structure of inner NPs consisting of PLA had a significant impact on the degradation profiles of NPs and the release/degradation behavior of encapsulated antigens and thus the efficiency of immune induction. Our findings suggest that the γ-PGA–PLA SC NPs are suitable for protein-based vaccines that are used to induce cellular immunity, such as for infectious diseases, cancer, allergies and autoimmune diseases.