一种自组装的抗原和针对树突状细胞的纳米疫苗,用于增强免疫力对抗癌症。
An antigen self-assembled and dendritic cell-targeted nanovaccine for enhanced immunity against cancer.
发表日期:2023 Aug
作者:
Yunting Zhang, Min Jiang, Guangsheng Du, Xiaofang Zhong, Chunting He, Ming Qin, Yingying Hou, Rong Liu, Xun Sun
来源:
Immunity & Ageing
摘要:
纳米技术的兴起为癌症免疫疗法开辟了新的前景。然而,大多数由纳米材料制造的纳米疫苗存在着载体相关的问题,包括低药物载荷能力、不可预测的代谢以及潜在的全身毒性,这给它们的临床转化带来了障碍。在此,我们开发了一种抗原自组装纳米疫苗,该疫苗是通过简单的丙烯酰改性抗原诱导自组装而成。此外,还将靶向树突状细胞的头部甘露糖单体和甲酮酸途径抑制剂左甲隆酸(Zol)整合或吸附到纳米颗粒上(简称MEAO-Z),以增强免疫应答。合成的纳米疫苗直径约为70nm,显示出成功的淋巴结转运、高树突状细胞内吞作用、促进辅助分子表达和较好的抗原交叉呈递。基于上述优势,MEAO-Z疫苗引起了明显更高的血清抗体滴度、更强的细胞毒性T淋巴细胞免疫应答和IFN-γ分泌,相比自由抗原和佐剂。体内,MEAO-Z显著抑制了EG7-OVA肿瘤的生长,并延长了携带肿瘤的小鼠的生存时间。这些结果表明我们自组装的纳米疫苗在免疫增强和癌症免疫疗法方面具有翻译潜力。© 2023 中国药学会和中国医学科学院药物研究所。由Elsevier B.V.进行生产和托管。
The rise of nanotechnology has opened new horizons for cancer immunotherapy. However, most nanovaccines fabricated with nanomaterials suffer from carrier-related concerns, including low drug loading capacity, unpredictable metabolism, and potential systemic toxicity, which bring obstacles for their clinical translation. Herein, we developed an antigen self-assembled nanovaccine, which was resulted from a simple acryloyl modification of the antigen to induce self-assembly. Furthermore, a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid (Zol) were integrated or absorbed onto the nanoparticles (denoted as MEAO-Z) to intensify the immune response. The synthesized nanovaccine with a diameter of around 70 nm showed successful lymph node transportation, high dendritic cell internalization, promoted costimulatory molecule expression, and preferable antigen cross-presentation. In virtue of the above superiorities, MEAO-Z induced remarkably higher titers of serum antibody, stronger cytotoxic T lymphocyte immune responses and IFN-γ secretion than free antigen and adjuvants. In vivo, MEAO-Z significantly suppressed EG7-OVA tumor growth and prolonged the survival time of tumor-bearing mice. These results indicated the translation promise of our self-assembled nanovaccine for immune potentiation and cancer immunotherapy.© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.