基于表面涂层益生菌的肿瘤抗原口服递送系统

林思思; 潘超; 张一帆; 刘尽尧

doi:10.12211/2096-8280.2022-010

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基于表面涂层益生菌的肿瘤抗原口服递送系统

研究论文 | 更新时间：2025-03-20

- 基于表面涂层益生菌的肿瘤抗原口服递送系统
- Coated probiotic-based drug carriers for oral delivery of tumor antigens
- 合成生物学 2022年3卷第4期页码：810-820
- 作者机构：
  
  1. 上海交通大学医学院附属仁济医院，上海市肿瘤研究所，上海　200011
  2. 上海交通大学医学院附属仁济医院，分子医学研究院，上海　200127
- 作者简介：
  
  [ "\t\t\t\t\t\t\t林思思（1990—），女，助理研究员。研究方向为肠屏障损伤防治、屏障生物医用材料等。E-mail：linsisi@renji.com\t\t\t\t\t\t" ]
  [ "\t\t\t\t\t\t\t潘超（1990—），男，助理研究员。研究方向为表面改性等。E-mail：pca123@mail.ustc.edu.cn\t\t\t\t\t\t" ]
  [ "\t\t\t\t\t\t\t刘尽尧（1983—），男，研究员，博士生导师。研究方向为新型生物医用高分子的可控制备、药物传递系统的生物制备新技术、智能仿生材料的生物合成新方法以及细菌改造与菌群调控介导的疾病治疗新策略等。E-mail：jyliu@sjtu.edu.cn\t\t\t\t\t\t" ]
- 基金信息：
  
  国家自然科学基金(21875135)
- DOI：10.12211/2096-8280.2022-010
  中图分类号： R392
- 收稿：2022-01-29，
  
  修回：2022-03-10，
  
  纸质出版：2022-08-31
- 稿件说明：
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林思思，潘超，张一帆，刘尽尧. 基于表面涂层益生菌的肿瘤抗原口服递送系统［J］. 合成生物学， 2022， 3（4）： 810-820

LIN Sisi， PAN Chao， ZHANG Yifan， LIU Jinyao. Coated probiotic-based drug carriers for oral delivery of tumor antigens［J］. Synthetic Biology Journal， 2022， 3（4）： 810-820
林思思，潘超，张一帆，刘尽尧. 基于表面涂层益生菌的肿瘤抗原口服递送系统［J］. 合成生物学， 2022， 3（4）： 810-820 DOI： 10.12211/2096-8280.2022-010.

LIN Sisi， PAN Chao， ZHANG Yifan， LIU Jinyao. Coated probiotic-based drug carriers for oral delivery of tumor antigens［J］. Synthetic Biology Journal， 2022， 3（4）： 810-820 DOI： 10.12211/2096-8280.2022-010.

摘要

肿瘤疫苗是一种通过递送肿瘤抗原进而激活自身特异性抗肿瘤免疫的肿瘤免疫疗法。口服具有方便、简单和高效的优势。然而现有的口服肿瘤疫苗有限，并且局限于胃肠道肿瘤的治疗。这主要与缺乏先进的口服递送载体有关。本研究设计了一种酵母细胞膜包覆的益生菌应用于口服递送系统。其中，酵母细胞膜发挥益生菌和抗原保护以及肠道淋巴系统靶向的作用；益生菌发挥搭载抗原和免疫佐剂的作用。结果显示，与裸菌相比，酵母细胞膜包覆能提高益生菌的生物利用度，增强其在派氏结的富集，促进树突状细胞的活化和抗原递呈以及小鼠血浆中OVA-IgG水平。实验证明该系统能够保护益生菌和抗原免受胃肠道环境刺激并进一步向肠道淋巴系统递送抗原，激活抗肿瘤免疫。

Abstract

Cancer vaccines

as a form of cancer immunotherapy

trigger host anti-tumor immunity by delivering tumor antigens. Oral administration has the advantages of convenience

simplicity and high efficacy. However

oral tumor vaccines have been rarely reported and existing forms are solely suitable for gastrointestinal cancer. The situation is associated with lack of advanced oral delivery systems. In this study

yeast cell membrane-coated probiotics are developed as drug carriers for oral delivery of tumor antigens. Yeast cell membranes play a dual role in protecting probiotics and antigens and facilitating targeted delivery of tumor antigens to the gut lymphatic system

while probiotics serve as both immune adjuvant and antigen carrier. As a model antigen

ovalbumin (OVA) is loaded onto probiotic surface by complexing with polyethyleneimine and hyaluronic acid

via

electrostatic interaction. Subsequently

antigen-loaded probiotics are individually camouflaged with yeast membranes by physical extrusion through a porous membrane. As reflected by similar growth to uncoated probiotics

both the coating and preparation procedures have limited influences on bacterial viability. Ex

perimental results show that

compared to unmodified bacteria

yeast cell membrane coated probiotics retain their ability to grow and divide after incubation in simulated gastrointestinal environments and exhibit an improved bioavailability following oral ingestion. The presence of embedded β-glucan on yeast membranes promotes the phagocytosis by microfold cells that locate in intestinal epithelium. After oral gavage

the coating facilitates the accumulation of wrapped probiotics in Peyer's patches and then in mesenteric lymph nodes. Furthermore

the maturation of dendritic cells and corresponding antigen presentation are enhanced by coated probiotics

which induce an OVA-specific immune response as manifested by an upgraded serum level of OVA-IgG in mice after oral administration. These results demonstrate that yeast cell membrane-coated probiotics show enhanced tolerance against insults in the gastrointestinal environment and improved delivery of antigens into the gut lymphatic system

hence activating anti-tumor immunity.

关键词

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references

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