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首页> 外文期刊>Acta biomaterialia >Functionalization of polyanhydride microparticles with di-mannose influences uptake by and intracellular fate within dendritic cells
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Functionalization of polyanhydride microparticles with di-mannose influences uptake by and intracellular fate within dendritic cells

机译：具有二甘露糖的聚酸酐微粒的功能化影响树突状细胞的摄取和细胞内命运

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Innovative vaccine delivery platforms can facilitate the development of effective single-dose treatment regimens to control emerging and re-emerging infectious diseases. Polyanhydride microparticles are promising vaccine delivery vehicles due to their ability to stably maintain antigens, provide tailored release kinetics and function as adjuvants. A major obstacle for the use of microparticle-based vaccines, however, is their limited uptake by dendritic cells (DCs). In this study, we functionalized the microparticle surface with di-mannose in order to target C-type lectin receptors (CLRs) on DCs. Polyanhydride particles based on sebacic acid (SA), 1,6-bis(p-carboxyphenoxy) hexane (CPH) and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) were evaluated. Co-incubation of di-mannose-functionalized microparticles up-regulated the expression of CLRs on DCs. More importantly, di-mannose functionalization increased the uptake, as measured by the percentage of cells internalizing particles. The uptake of CPH:SA microparticles increased ～20-fold, from 0.82% (non-functionalized) to 20.2%, and internalization of CPTEG:CPH microparticles increased ～7-fold from 1.35% (non-functionalized) to 9.3% upon di-mannose functionalization. Both di-mannose-functionalized and non-functionalized particles trafficked to lysosomes. Together, these studies demonstrate that employing rational vaccine design principles, such as the targeting of CLRs on antigen-presenting cells, can enhance delivery of encapsulated antigens and potentially induce a more robust adaptive immune response.
机译：创新的疫苗输送平台可以促进有效的单剂量治疗方案的开发，以控制正在出现和重新出现的传染病。聚酸酐微粒由于其稳定地维持抗原，提供定制的释放动力学和作为佐剂的能力而成为有希望的疫苗递送载体。但是，使用基于微粒的疫苗的主要障碍是树突状细胞（DC）对它们的摄取有限。在这项研究中，我们用二甘露糖功能化了微粒表面，以靶向DC上的C型凝集素受体（CLR）。评估了基于癸二酸（SA），1,6-双（对羧基苯氧基）己烷（CPH）和1,8-双（对羧基苯氧基）-3,6-二氧八辛烷（CPTEG）的聚酸酐颗粒。二甘露糖功能化的微粒的共同孵育上调了DC上CLR的表达。更重要的是，二甘露糖功能化增加了摄取，这是通过细胞内化颗粒的百分比来衡量的。 CPH：SA微粒的摄取量增加了约20倍，从0.82％（未官能化）增加到20.2％，而CPTEG：CPH微粒的内在化从5％增加了7倍，从1.35％（未官能化）增加到9.3％。 -甘露糖功能化。二甘露糖官能化的颗粒和非官能化的颗粒均运至溶酶体。总之，这些研究表明，采用合理的疫苗设计原则，例如将CLR靶向抗原呈递细胞，可以增强封装抗原的递送，并可能诱导更强的适应性免疫应答。

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