Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, China.
Department of Laboratory Medicine, General Hospital of Southern Theatre Command of PLA, Guangzhou 510010, China.
J Mater Chem B. 2022 May 11;10(18):3474-3490. doi: 10.1039/d1tb02650j.
In the field of tumor immunotherapy, tumor vaccines have unique advantages including fewer side effects, tumor-specificity and immune memory, and hence attract more and more attention. In the development of tumor vaccines, a critical challenge lies in the exploitation of appropriate vaccine adjuvants/delivery systems that need to meet multiple requirements to achieve potent cellular immunity while simultaneously requiring single composition to simplify the clinical translation process. Among numerous materials, only manganese dioxide (MnO) nanoparticles with rare physicochemical properties seem to meet the demanding criteria of simplicity and multifunctionality. However, the potential of MnO nanoparticles as vaccine adjuvants/delivery systems has not been well exploited, despite their widespread applications in the biomedical field. In this study, the mechanism and efficacy of single MnO nanoparticles as a minimalist multi-mode tumor vaccine adjuvant/delivery system were fully investigated by using a model antigen ovalbumin (OVA) to construct tumor vaccines OVA/MnO. The obtained results show that MnO nanoparticles act as an ideal delivery system by multiple modes to deliver the antigen to the cytoplasm of dendritic cells to induce cellular immune response. Moreover, MnO nanoparticles also act as a superior adjuvant depot to sustainably release Mn to enhance the immune response through a STING pathway in dendritic cells. Both the delivery function and the adjuvant effect of MnO nanoparticles contribute to improved cellular immunity and anti-tumor efficacy of tumor vaccines OVA/MnO. From the results, MnO nanoparticles are found to be a promising minimalist multi-mode vaccine adjuvant/delivery system for the development of practical tumor vaccines.
在肿瘤免疫治疗领域，肿瘤疫苗具有副作用少、肿瘤特异性和免疫记忆等独特优势，因此越来越受到关注。在肿瘤疫苗的开发中，一个关键的挑战在于开发合适的疫苗佐剂/递送系统，这些系统需要满足多种要求，以实现有效的细胞免疫，同时要求单一成分以简化临床转化过程。在众多材料中，只有具有罕见物理化学性质的二氧化锰（MnO）纳米粒子似乎满足了简单性和多功能性的苛刻标准。然而，尽管 MnO 纳米粒子在生物医学领域有广泛的应用，但它们作为疫苗佐剂/递送系统的潜力尚未得到充分开发。在本研究中，我们通过使用模型抗原卵清蛋白（OVA）构建肿瘤疫苗 OVA/MnO，全面研究了单 MnO 纳米粒子作为极简多模式肿瘤疫苗佐剂/递送系统的作用机制和效果。研究结果表明，MnO 纳米粒子通过多种模式充当理想的递送系统，将抗原递送至树突状细胞的细胞质中，从而诱导细胞免疫反应。此外，MnO 纳米粒子还充当了优异的佐剂库，通过树突状细胞中的 STING 途径持续释放 Mn 以增强免疫反应。MnO 纳米粒子的递送功能和佐剂作用都有助于提高肿瘤疫苗 OVA/MnO 的细胞免疫和抗肿瘤功效。总之，MnO 纳米粒子有望成为一种有前途的极简多模式疫苗佐剂/递送系统，用于开发实用的肿瘤疫苗。
