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Alum-functionalized graphene oxide nanocomplexes for effective anticancer vaccination.
Acta Biomaterialia ( IF 9.7 ) Pub Date : 2018-11-15 , DOI: 10.1016/j.actbio.2018.11.023
Xiaoli Wang 1 , Fengqiang Cao 1 , Mengmeng Yan 1 , Yijia Liu 1 , Xianghui Zhu 1 , Hongfan Sun 1 , Guilei Ma 1
Affiliation  

Aluminum-based adjuvant (e.g., aluminum oxyhydroxide (AlO(OH), known as the commercial Alhydrogel® (Alum)) is the first adjuvant to be used in human vaccines. Although Alum shows a robust induction of antibody-mediated immunity, its weak stimulation of cell-mediated immunity makes it a questionable adjuvant for cancer immunotherapy. Herein, we described a novel formulation of Alum-based adjuvant by preparing AlO(OH)-modified graphene oxide (GO) nanosheets (GO-AlO(OH)), which, in addition to maintaining the induction of humoral immune response by AlO(OH), could further elicit the cellular immune response by GO. Similar to Alum, GO-AlO(OH) vaccine formulation could be constructed by the incorporation of antigen using a facile mixing/adsorption approach. Antigen-loaded GO-AlO(OH) nanocomplexes facilitated cellular uptake and cytosolic release of antigens and promoted DC maturation, thereby eliciting higher antigen-specific IgG titers, inducing robust CD4+ and CD8+ T lymphocyte response, and inhibiting tumor growth in vivo. Furthermore, by employing tumor cell lysate-based cancer vaccines, GO-AlO(OH) nanocomplexes led to significant inhibition of tumor growth and can be implemented as a personalized treatment strategy for cancer vaccine development. Overall, GO-AlO(OH) nanocomplexes described herein may serve as a facile and efficient approach for effective anticancer vaccination. STATEMENT OF SIGNIFICANCE: Herein, we described a novel formulation of aluminum-based adjuvant by preparing aluminum oxyhydroxide (AlO(OH)) (known as "Alum")-modified graphene oxide (GO) nanocomplexes (GO-AlO(OH)), which, in addition to maintaining the induction of humoral immune response by AlO(OH), could further elicit the cellular immune response by GO. GO-AlO(OH) nanocomplexes can be prepared easily and in large scale by a chemical precipitation method. Similar to "Alum," antigen-loaded GO-AlO(OH) vaccine formulation could be constructed by the incorporation of antigen using a facile mixing/adsorption approach. The very simple and reproductive preparation process of vaccines and the powerful ability to raise both humoral and cellular immune responses provide a novel approach for improving cancer immunotherapy efficacy.

中文翻译:

明矾功能化的氧化石墨烯纳米复合物,可有效进行抗癌疫苗接种。

载有抗原的GO-AlO(OH)纳米复合物促进了抗原的细胞吸收和胞质释放并促进了DC成熟,从而引发了更高的抗原特异性IgG滴度,诱导了强劲的CD4 +和CD8 + T淋巴细胞反应,并抑制了体内肿瘤的生长。此外,通过使用基于肿瘤细胞裂解物的癌症疫苗,GO-AlO(OH)纳米复合物可显着抑制肿瘤生长,并可作为癌症疫苗开发的个性化治疗策略来实施。总体而言,本文所述的GO-AlO(OH)纳米复合物可用作有效的抗癌疫苗接种的简便且有效的方法。重要性说明:在此,我们通过制备氢氧化铝(AlO(OH))(称为“明矾”)描述了一种新型的铝基助剂配方。)修饰的氧化石墨烯(GO)纳米复合物(GO-AlO(OH)),除了维持AlO(OH)诱导的体液免疫反应外,还可以进一步引发GO引起的细胞免疫反应。GO-AlO(OH)纳米复合物可以通过化学沉淀法轻松,大规模地制备。类似于“明矾”,可以通过使用简便的混合/吸附方法掺入抗原来构建载有抗原的GO-AlO(OH)疫苗制剂。疫苗的非常简单和生殖的制备过程,以及增强体液和细胞免疫反应的强大能力,为提高癌症免疫疗法的有效性提供了一种新颖的方法。GO-AlO(OH)纳米复合物可以通过化学沉淀法轻松,大规模地制备。类似于“明矾”,可以通过使用简便的混合/吸附方法掺入抗原来构建载有抗原的GO-AlO(OH)疫苗制剂。疫苗的非常简单和生殖的制备过程,以及增强体液和细胞免疫反应的强大能力,为提高癌症免疫疗法的有效性提供了一种新颖的方法。GO-AlO(OH)纳米复合物可以通过化学沉淀法轻松,大规模地制备。类似于“明矾”,可以通过使用简便的混合/吸附方法掺入抗原来构建载有抗原的GO-AlO(OH)疫苗制剂。疫苗的非常简单和生殖的制备过程,以及增强体液和细胞免疫反应的强大能力,为提高癌症免疫疗法的有效性提供了一种新颖的方法。
更新日期:2018-11-15
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