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具有 T1/T2MRI 自导航和气体生成功能的通用 Fe/Mn 纳米佐剂,用于具有精确跟踪的理想疫苗。

Universal Fe/Mn Nanoadjuvant with T1/T2 MRI Self-Navigation and Gas Generation for Ideal Vaccines with Precise Tracking.

机构信息

Department of Oncology, The First Affiliated Hospital and Department of Chemistry, Jinan University, Guangzhou 510632, China.

出版信息

ACS Nano. 2023 Aug 22;17(16):15590-15604. doi: 10.1021/acsnano.3c02309. Epub 2023 Aug 2.

Abstract

Because of the distinguished properties between nanovaccine and traditional vaccine, the precise guidelines for nanovaccines with an optimal vaccination strategy to induce ideal immunities are greatly desired for combating major diseases, including cancer and infections. Herein, we designed and synthesized a self-navigating nanoadjuvant composed of Fe-doped manganese carbonate and its nanovaccine via a facile method. First, the degradation of the nanoadjuvant under acidic milieu of immune cells in lymph nodes would generate T1 and T2 MR imaging (MRI) signals to reflect the transformation dynamics of the nanovaccine and inform us when the next vaccination needed. Under this guideline, nanovaccines with a precise vaccination strategy triggered robust antigen-specific immune responses and immunological memory to effectively prevent ovalbumin (OVA)-expressing melanoma relapse by activating dendritic cells via a stimulator of interferon genes (STING) signaling pathway and inducing antigen cross-presentation by shaping lysosome integrity with CO generation and upregulating transporter associated antigen processing 1 (TAP-1) transporter. This study provides a universal nanoadjuvant with imaging self-guidance, immunopotentiating, and cross-priming activities for developing precise vaccines with an optimal immunization strategy to combat major diseases.

摘要

由于纳米疫苗具有独特的性质,因此需要制定精确的指导方针,以优化接种策略,从而诱导理想的免疫反应,以对抗癌症和感染等重大疾病。在此,我们通过简便的方法设计并合成了由掺铁碳酸锰组成的自导航纳米佐剂及其纳米疫苗。首先,纳米佐剂在淋巴结免疫细胞的酸性环境下降解,会产生 T1 和 T2 磁共振成像(MRI)信号,以反映纳米疫苗的转化动态,并提示何时需要进行下一次接种。根据这一指导方针,采用精确的接种策略的纳米疫苗可通过干扰素基因刺激物(STING)信号通路激活树突状细胞,并通过生成 CO 来维持溶酶体完整性、上调转运体相关抗原加工 1(TAP-1)转运体,从而诱导抗原交叉呈递,引发强烈的抗原特异性免疫反应和免疫记忆,有效预防卵清蛋白(OVA)表达的黑色素瘤复发。本研究提供了一种具有成像自我指导、免疫增强和交叉呈递活性的通用纳米佐剂,可用于开发具有最佳免疫策略的精确疫苗,以对抗重大疾病。

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