Hollow Mesoporous Silica Nanoparticles with Extra-Large Mesopores for Enhanced Cancer Vaccine.,ACS Applied Materials & Interfaces

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Hollow Mesoporous Silica Nanoparticles with Extra-Large Mesopores for Enhanced Cancer Vaccine.
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2020-07-14 , DOI: 10.1021/acsami.0c09484
Jun Yup Lee ₁ , Min Kyung Kim ₂ , Thanh Loc Nguyen ₁ , Jaeyun Kim _{1,

2,

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Affiliation

Owing to the limitations of conventional cancer therapies, cancer immunotherapy has emerged for the prevention of cancer recurrence. To provoke adaptive immune responses that are antigen-specific, it is important to develop an efficient antigen delivery system that can enhance the activation and maturation of the dendritic cells (DCs) in the human body. In this study, we synthesize hollow mesoporous silica nanoparticles with extra-large mesopores (H-XL-MSNs) based on a single-step synthesis from core–shell mesoporous silica nanoparticles with a core composed of an assembly of iron oxide nanoparticles. The hollow void inside the mesoporous silica nanoparticles with large mesopores allows a high loading efficiency of various model proteins of different sizes. The H-XL-MSNs are coated with a poly(ethyleneimine) (PEI) solution to provide an immune adjuvant and change the surface charge of the particles for loading and slow release of a model antigen. An in vitro study using a cancer vaccine based on the PEI-coated H-XL-MSNs with the loading of the model antigen showed an enhanced activation of the DCs. An in vivo study demonstrated that the resulting cancer vaccine increased the antigen-specific cytotoxic T cells, enhanced the suppression of tumor growth, and improved the survival rate after challenging cancer to mice. These findings suggest that these hollow MSNs with extra-large pores can be used as excellent antigen carriers for immunotherapy.

中文翻译：

具有超大中孔的中孔二氧化硅纳米颗粒，用于增强癌症疫苗。

由于常规癌症疗法的局限性，已经出现了用于预防癌症复发的癌症免疫疗法。为了激发抗原特异性的适应性免疫应答，重要的是开发一种有效的抗原递送系统，该系统可以增强人体中树突状细胞（DC）的激活和成熟。在这项研究中，我们基于核-壳介孔二氧化硅纳米粒子的一步合成，合成了具有超大介孔（H-XL-MSNs）的空心介孔二氧化硅纳米粒子。具有大中孔的中孔二氧化硅纳米粒子内部的空心空间允许不同大小的各种模型蛋白质具有较高的加载效率。H-XL-MSN涂有聚乙烯亚胺（PEI）溶液，可提供免疫佐剂并改变颗粒的表面电荷，以加载和缓慢释放模型抗原。一项使用基于PEI涂层的H-XL-MSN并带有模型抗原负载的癌症疫苗进行的体外研究显示，DC的激活增强。一项体内研究表明，所得的癌症疫苗可增加抗原特异性细胞毒性T细胞，增强对肿瘤生长的抑制作用，并提高了向小鼠攻击癌症后的存活率。这些发现表明，这些具有超大孔的空心MSN可以用作免疫治疗的优良抗原载体。一项使用基于PEI涂层的H-XL-MSN并带有模型抗原负载的癌症疫苗进行的体外研究显示，DC的激活增强。一项体内研究表明，所得的癌症疫苗可增加抗原特异性细胞毒性T细胞，增强对肿瘤生长的抑制作用，并提高了向小鼠攻击癌症后的存活率。这些发现表明，这些具有超大孔的空心MSN可以用作免疫治疗的优良抗原载体。一项使用基于PEI涂层的H-XL-MSN并带有模型抗原负载的癌症疫苗进行的体外研究显示，DC的激活增强。一项体内研究表明，所得的癌症疫苗可增加抗原特异性细胞毒性T细胞，增强对肿瘤生长的抑制作用，并提高了向小鼠攻击癌症后的存活率。这些发现表明，这些具有超大孔的空心MSN可以用作免疫疗法的优良抗原载体。

更新日期：2020-08-05

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