苏州大学碳基功能材料与器件江苏省重点实验室陈倩团队近期取得重要工作进展，他们研究开发了一种新型抗菌纳米疫苗，通过选择性清除肿瘤定植细菌来增强化疗效果。相关研究成果2024年6月14日在线发表于《科学通报》杂志上。

据介绍，核酸杆菌是一种口腔厌氧菌，在结直肠癌癌症中普遍存在，与癌症细胞生长、转移和不良治疗结果密切相关。能够选择性消除细菌的细菌疫苗，为靶向瘤内核酸杆菌提供了一种很有希望的方法，从而增强癌症的治疗。尽管佐剂已被用于增强免疫反应，但疫苗的有效性受到根除细胞内病原体所需的T细胞活化不足的限制。

研究人员通过将高度免疫刺激的佐剂胆固醇修饰的CpG寡核苷酸，整合到同源的核酸杆菌膜中，开发了一种最小限度的仿生纳米疫苗。与灭活细菌和明矾佐剂组成的传统疫苗相比，与细菌膜和佐剂偶联的纳米疫苗可以显著改善，多种抗原和佐剂向树突状细胞的共递送，最大限度地提高其实现有效抗原呈递和强大下游免疫进展的能力。

纳米疫苗表现出突出的选择性预防和治疗效果，在不影响肿瘤内和肠道微生物群的情况下消除了核酸杆菌。疫苗显著提高了有核大肠杆菌感染癌症的化疗效果，并减少了癌症转移。

总之，这一工作代表了细菌纳米疫苗的合理应用，并为增强对细菌感染的癌症的抗肿瘤作用提供了未来发展的蓝图。

附：英文原文

Title: An emerging antibacterial nanovaccine for enhanced chemotherapy by selectively eliminating tumor-colonizing bacteria

Author: Qian Chen a

Issue&Volume: 2024/06/14

Abstract: Fusobacterium nucleatum (F. nucleatum), an oral anaerobe, is prevalent in colorectal cancer and is closely related to increased cancer cell growth, metastasis, and poor treatment outcomes. Bacterial vaccines capable of selectively eliminating bacteria present a promising approach to targeting intratumor F. nucleatum, thereby enhancing cancer treatment. Although adjuvants have been employed to enhance the immune response, the vaccine’s effectiveness is constrained by inadequate T-cell activation necessary for eradicating intracellular pathogens. In this study, we developed a minimalistic, biomimetic nanovaccine by integrating highly immunostimulatory adjuvant cholesterol-modified CpG oligonucleotides into the autologously derived F. nucleatum membranes. Compared to the traditional vaccines consisting of inactivated bacteria and Alum adjuvant, the nanovaccine coupled with bacterial membranes and adjuvants could remarkably improve multiple antigens and adjuvant co-delivery to dendritic cells, maximizing their ability to achieve effective antigen presentation and strong downstream immune progress. Notably, the nanovaccine exhibits outstanding selective prophylactic and therapeutic effects, eliminating F. nucleatum without affecting intratumoral and gut microbiota. It significantly enhances chemotherapy efficacy and reduces cancer metastasis in F. nucleatum-infected colorectal cancer. Overall, this work represents the rational application of bacterial nanovaccine and provides a blueprint for future development in enhancing the antitumor effect against bacterial-infected cancer.

DOI: 10.1016/j.scib.2024.06.016

Source: https://www.sciencedirect.com/science/article/abs/pii/S2095927324004274