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

一种新型细菌纳米疫苗通过选择性清除肿瘤定植细菌增效肿瘤化疗

作　　者：Linfu Chen Zheyu Kang Jingjing Shen Rui Zhao Yu Miao Lin Zhang Zixuan Zheng Zhemin Zhang Nanhui Liu Cheng Wang Huapan Fang Jun Zhou Yudong Wang Zhuang Liu Yang Yang Qian Chen 陈林甫;康哲雨;沈菁菁;赵蕊;缪雨;张琳;郑紫萱;张哲民;刘南辉;王成;方华攀;周骏;王玉东;刘庄;杨洋;陈倩

机构地区：[1]Institute of Functional Nano&Soft Materials(FUNSOM),Jiangsu Key Laboratory for Carbon-Based Functional Materials&Devices,Soochow University,Suzhou 215123,China [2]Department of Gynecologic Oncology,The International Peace Maternity and Child Health Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200030,China [3]Department of Thoracic Surgery,Shanghai Pulmonary Hospital,Tongji University School of Medicine,Shanghai 200433,China

出　　处：《Science Bulletin》2024年第16期2565-2579,共15页科学通报（英文版）

基　　金：partially supported by the National Research Programs of China(2022YFA1206500 and 2020YFA0211100);the National Natural Science Foundation of China(52172285 and 52325106);the Suzhou Key Laboratory of Nanotechnology and Biomedicine,the Collaborative Innovation Centre of Suzhou Nano Science and Technology;the 111 Program from the Ministry of Education of China.

摘　　要：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.

关 键 词：Fusobacterium nucleatum Bacterial vaccine Colorectal cancer Biomimetic nanomedicine CHEMOTHERAPY 

分 类 号：R730.51[医药卫生—肿瘤] TB383.1[医药卫生—临床医学]