细菌及其递送载体在抗肿瘤治疗中的研究进展  

Research Progress on Bacteria and Their Delivery Vectors in Anti-tumor Therapy

作　　者：付恬恬 林玉红 赵凯[1,2] FU Tiantian;LIN Yuhong;ZHAO Kai(Engineering Research Center of Agricultural Microbiology Technology of Ministry of Education,Heilongjiang Provincial Key Laboratory of Plant Genetic Engineering and Biological Fermentation Engineering for Cold Region,School of Life Sciences,Heilongjiang University,Harbin 150080,China;Zhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation,Taizhou Key Laboratory of Biomedicine and Advanced Dosage Forms,School of Life Sciences,Taizhou University,Taizhou 318000,China)

机构地区：[1]黑龙江大学生命科学学院、农业微生物技术教育部工程研究中心、黑龙江省寒区植物基因与生物发酵重点实验室,哈尔滨150080 [2]台州学院生命科学学院、浙江省植物进化生态学与保护重点实验室、台州市生物医药与高端剂型重点实验室,台州318000

出　　处：《中国生物工程杂志》2025年第2期94-103,共10页China Biotechnology

基　　金：浙江省自然科学基金联合基金(LKLY25H180008);台州市科技计划(23gya01)资助项目。

摘　　要：癌症是一种严重威胁人类健康的疾病,传统的治疗手段如化疗和放疗等虽具有较好治疗效果,但在临床上也表现出较明显的副作用。自美国学者William Coley使用化脓性链球菌缓解肉瘤的研究发表后,由于天然细菌具有自我推进和群体感应的能力,而肿瘤细胞内的氧浓度梯度保证细菌的定向迁移,营养物质的富集也保证了细菌增殖而不会被免疫系统消灭,细菌重新被用作治疗肿瘤的手段。细菌能导致肿瘤细胞死亡,但同时也会抑制宿主的免疫反应,损害机体对肿瘤的免疫效果,因此用于抗肿瘤治疗的细菌需要经过基因工程改造,如删除毒力因子基因或在细菌细胞壁前添加启动子保证其在缺氧条件下才会达到致死条件。此外,细菌还可作为药物的递送载体靶向治疗肿瘤,以达到高效精准地药物控释。综述了细菌及其作为递送载体在抗肿瘤治疗中的应用,详细介绍了细菌基因工程降低自身毒性的方案以及细菌载体与其他抗肿瘤疗法的联合应用,并为未来可能的研究提供了优化后更安全、高效的治疗方案。Cancer is a serious threat to human health,and although traditional treatment methods such as chemotherapy and radiotherapy have good therapeutic effects,they also show obvious side effects in clinical practice.Since the publication of American scientist William Coley’s study using Streptococcus pyogenes to alleviate sarcoma,bacteria have been reused as a means of treating tumors because natural bacteria have the ability to self-propagate and quorum sensing,the oxygen concentration gradient within tumor cells ensures the directional migration of bacteria,and the enrichment of nutrients also ensures that bacteria proliferate without being destroyed by the immune system.Bacteria can cause tumor cell death,but at the same time,they can inhibit the host’s immune response and interfere with the body’s immune effect against tumors,so bacteria used for anti-tumor therapy must be genetically engineered,such as deleting virulence factor genes or adding promoters to the bacterial cell walls to ensure that they can only reach lethal conditions under hypoxic conditions.Bacteria can also be used as drug delivery vehicles to target tumors for efficient and precise drug delivery.This article reviews bacteria and their application as delivery vectors in anti-tumor therapy,introduces in detail the protocol of bacterial genetic engineering to reduce autotoxicity and the combination application of bacterial vectors with other anti-tumor therapies,and provides an optimized,safer and more efficient treatment option for possible future research.

关 键 词：细菌 递送载体 基因工程 抗肿瘤治疗 

分 类 号：Q812[生物学—生物工程]