Metal–Phenolic Network-Encapsulated Nanovaccine with pH and Reduction Dual Responsiveness for Enhanced Cancer Immunotherapy,Molecular Pharmaceutics

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Metal–Phenolic Network-Encapsulated Nanovaccine with pH and Reduction Dual Responsiveness for Enhanced Cancer Immunotherapy
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-11-11 , DOI: 10.1021/acs.molpharmaceut.0c00802
Xin Zhou ₁ , Qianhong Su ₁ , Hongwei Zhao ₂ , Xianying Cao ₁ , Yong Yang ₁ , Wei Xue ₃

Affiliation

Cancer nanovaccines have been widely explored to enhance immunotherapy efficiency, in which the significant irritation of antigen-specific cytotoxic T cells (CTLs) is the critical point. In this study, we developed a pH and reduction dual-sensitive nanovaccine (PMSN@OVA-MPN) composed of two parts. The inner part was made up of polyethyleneimine (PEI)-modified mesoporous silica nanoparticles (MSNs) loaded with model antigen ovalbumin (OVA) and the outer part was made up of disulfide bond-involved metal–phenolic networks (MPNs) as a protective corona. In vitro release experiments proved that PMSN@OVA-MPN could intelligently release OVA in the presence of reductive glutathione, but not in neutral phosphate-buffered saline (PBS). Moreover, in vitro cell assays indicated that the nanovaccine promoted not only the OVA uptake efficiency by DC2.4 cells but also antigen lysosome escape due to the proton sponge effect of PEI. Furthermore, in vivo animal experiments indicated that PMSN@OVA-MPN induced a large tumor-specific cellular immune response so as to effectively inhibit the growth of an existing tumor. Finally, the immune memory effect caused by the nanovaccine afforded conspicuous prophylaxis efficacy in neonatal tumors. Hence, the multifunctional vaccine delivery system prepared in this work exhibits a great application potential in cancer immunotherapy and offers a platform for the development of nanovaccines.

中文翻译：

具有 pH 值和还原双重响应的金属-酚醛网络封装纳米疫苗用于增强癌症免疫治疗

癌症纳米疫苗已被广泛探索以提高免疫治疗效率，其中抗原特异性细胞毒性 T 细胞 (CTL) 的显着刺激是关键点。在这项研究中，我们开发了一种由两部分组成的 pH 和还原双敏感纳米疫苗 (PMSN@OVA-MPN)。内部由聚乙烯亚胺 (PEI) 修饰的介孔二氧化硅纳米粒子 (MSNs) 组成，该纳米粒子加载有模型抗原卵清蛋白 (OVA)，外部由二硫键参与的金属 - 酚网络 (MPNs) 作为保护电晕组成. 体外释放实验证明，PMSN@OVA-MPN在还原性谷胱甘肽存在的情况下可以智能地释放OVA，但在中性磷酸盐缓冲盐水（PBS）中则不然。此外，体外细胞测定表明，纳米疫苗不仅促进 DC2.4 细胞对 OVA 的吸收效率，而且由于 PEI 的质子海绵效应，还促进了抗原溶酶体的逃逸。此外，体内动物实验表明，PMSN@OVA-MPN诱导了大量的肿瘤特异性细胞免疫反应，从而有效抑制了现有肿瘤的生长。最后，纳米疫苗引起的免疫记忆效应在新生儿肿瘤中提供了显着的预防效果。因此，本工作制备的多功能疫苗递送系统在癌症免疫治疗中具有巨大的应用潜力，并为纳米疫苗的开发提供了平台。

更新日期：2020-11-11

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