A strategy for enhanced tumor targeting of photodynamic therapy based on Escherichia coli-driven drug delivery system  

一种基于大肠杆菌驱动药物递送系统增强光动力治疗的肿瘤靶向策略

作　　者：Tao Dai Farong Ye Ping Hu Xiaohong Pan Jincan Chen Yunmei Huang Huanhuan Wang Lei Zhang Mingdong Huang Jianyong Liu Jianqiang Su Xueyuan Chen Zhuo Chen 戴涛;叶发荣;胡萍;潘小宏;陈锦灿;黄云梅;王欢欢;张蕾;黄明东;刘见永;苏建强;陈学元;陈卓(State Key Laboratory of Structural Chemistry,CAS Key Laboratory of Design and Assembly of Functional Nanostructures,Fujian Institute of Research on the Structure of Matter,Chinese Academy of Sciences,Fuzhou,350002,China;College of Chemistry,Fuzhou University,Fuzhou,350116,China;Academy of Integrative Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou,350122,China;Key Lab of Urban Environment and Health,Institute of Urban Environment,Chinese Academy of Sciences,Xiamen,361021,China;University of Chinese Academy of Sciences,Beijing,100049,China)

机构地区：[1]State Key Laboratory of Structural Chemistry,CAS Key Laboratory of Design and Assembly of Functional Nanostructures,Fujian Institute of Research on the Structure of Matter,Chinese Academy of Sciences,Fuzhou,350002,China [2]College of Chemistry,Fuzhou University,Fuzhou,350116,China [3]Academy of Integrative Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou,350122,China [4]Key Lab of Urban Environment and Health,Institute of Urban Environment,Chinese Academy of Sciences,Xiamen,361021,China [5]University of Chinese Academy of Sciences,Beijing,100049,China

出　　处：《Science China Materials》2021年第1期232-240,共9页中国科学（材料科学（英文版）

基　　金：supported by the National Natural Science Foundation of China (81572944, 21471033, 21877113 and 81971983);the CAS/SAFEA International Partnership Program for Creative Research Teams, the High-Level Entrepreneurship and Innovation Talents Projects in Fujian Province (2018-8-1);the FJIRSM&IUE Joint Research Fund (RHZX-2018-004)。

摘　　要：Escherichia coli(E. coli) DH5α has been recognized as a non-pathogenic bacterial strain with tumor colonization ability. However, whether such a bacteria-driven drug-delivery system can improve the targeting of tumor therapy or not remains essentially untouched. Herein, a series of zinc phthalocyanine(ZnPc) photosensitizers with different numbers of charges were prepared and their electrostatic adhesion properties on E. coli were investigated via measuring their fluorescence intensities by flow cytometer. Among these ZnPc photosensitizers investigated, the ZnPc conjugate with four positive charges(named ZnPc-IR710) exhibited the highest loading capacity and the best fluorescence imaging performance of E. coli. With the help of E. coli, E. coli@ZnPcIR710 presented a significantly enhanced cytotoxicity on human breast cancer MCF-7 cells compared with ZnPc-IR710(survival rate of tumor cells was 39% vs. 57% at a concentration of 50 nmol L-1). Moreover, in vivo study showed that E. coli@ZnPc-IR710 remarkably inhibited the tumor growth and resulted in a complete tumor growth suppress in subcutaneous mouse 4T1 breast tumor model. These results demonstrated the great promise of bacterial-guided photodynamic therapy(PDT) in the treatment of solid tumors, and provide a unique strategy to enhance the antitumor efficacy of PDT by utilizing bacterial vectors in tumors.大肠杆菌(简称E. coli) DH5α被认为是具有肿瘤定植能力的非致病菌,然而这种细菌驱动的药物传递系统能否提高肿瘤治疗的靶向性却鲜有报道.本文中,我们通过制备一系列带有不同电荷数的酞菁锌(ZnPc)光敏剂,研究了它们在大肠杆菌上的静电黏附特性,并借助流式细胞仪检测了其荧光强度.在所研究的ZnPc光敏剂中,带有4个正电荷的酞菁光敏剂ZnPc-IR710对E. coli具有最高的载药量和最佳的荧光成像性能.实验结果表明,与没有E. coli的ZnPc-IR710比较, E. coli@ZnPc-IR710对人乳腺癌MCF-7细胞的细胞毒性显著增强(同样条件下,该肿瘤细胞的存活率分别为39%(50 nmol L-1E. coli@ZnPc-IR710)和57%(ZnPc-IR710).此外,在体药理实验研究表明, E. coli@ZnPc-IR710对小鼠4T1皮下乳腺肿瘤的生长具有明显抑制作用,可完全抑制肿瘤生长.这些实验结果显示了利用细菌作为药物驱动传递系统在光动力疗法治疗实体肿瘤中的巨大潜力,同时也为增强光动力疗法的靶向抗肿瘤作用提供了独特策略.

关 键 词：PHOTOSENSITIZER zinc phthalocyanine bacteria-driven drug delivery system E.coli DH5α fluorescent molecular tomography 

分 类 号：R943[医药卫生—药剂学] TQ460.4[医药卫生—药学]