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中空氧化铝羟基化改性二氧化硅纳米佐剂通过诱导免疫原性细胞死亡和抗原释放增强免疫治疗效果。

Hollow Aluminum Hydroxide Modified Silica Nanoadjuvants with Amplified Immunotherapy Effects through Immunogenic Cell Death Induction and Antigen Release.

机构信息

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.

School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China.

出版信息

Small. 2022 Aug;18(34):e2202462. doi: 10.1002/smll.202202462. Epub 2022 Jul 27.

DOI:10.1002/smll.202202462
PMID:35896867
Abstract

In spite of the widespread application of vaccine adjuvants in various preventive vaccines at present, the existing adjuvants are still hindered by weak cellular immunity responses in therapeutic cancer vaccines. Herein, a hollow silica nanoadjuvant containing aluminum hydroxide spikes on the surface (SiAl) is synthesized for the co-loading of chemotherapeutic drug doxorubicin (Dox) and tumor fragment (TF) as tumor antigens (SiAl@Dox@TF). The obtained nanovaccines show significantly elevated anti-tumor immunity responses thanks to silica and aluminum-based composite nanoadjuvant-mediated tumor antigen release and Dox-induced immunogenic cell death (ICD). In addition, the highest frequencies of dendritic cells (DCs), CD4 T cells, CD8 T cells, and memory T cells as well as the best mice breast cancer (4T1) tumor growth inhibitory are also observed in SiAl@Dox@TF group, indicating favorable potential of SiAl nanoadjuvants for further applications. This work is believed to provide inspiration for the design of new-style nanoadjuvants and adjuvant-based cancer vaccines.

摘要

尽管目前疫苗佐剂在各种预防性疫苗中得到了广泛应用,但现有的佐剂仍受到治疗性癌症疫苗中细胞免疫应答较弱的限制。在此,合成了一种表面带有铝氢氧化物刺的中空硅纳米佐剂(SiAl),用于共载化疗药物阿霉素(Dox)和肿瘤片段(TF)作为肿瘤抗原(SiAl@Dox@TF)。由于硅基和铝基复合纳米佐剂介导的肿瘤抗原释放和 Dox 诱导的免疫原性细胞死亡(ICD),所得纳米疫苗显示出明显增强的抗肿瘤免疫应答。此外,在 SiAl@Dox@TF 组中还观察到树突状细胞(DCs)、CD4 T 细胞、CD8 T 细胞和记忆 T 细胞的最高频率,以及对小鼠乳腺癌(4T1)肿瘤生长的最佳抑制作用,表明 SiAl 纳米佐剂具有良好的应用潜力。这项工作为新型纳米佐剂和基于佐剂的癌症疫苗的设计提供了启示。

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