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A strategy for enhanced tumor targeting of photodynamic therapy based on Escherichia coli -driven drug delivery system
Science China Materials ( IF 6.8 ) Pub Date : 2020-07-09 , DOI: 10.1007/s40843-020-1363-2
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

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@ZnPc-IR710 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.



中文翻译:

基于大肠杆菌驱动的药物传递系统的光动力疗法增强肿瘤靶向性的策略

大肠埃希氏菌E. coli)DH5α被认为是具有肿瘤定殖能力的非致病性细菌菌株。然而,这种细菌驱动的药物递送系统是否可以改善肿瘤治疗的靶向性仍然基本未触及。此处,一系列具有不同数量的电荷的锌酞菁(酞菁锌)光敏剂的制备和它们的静电粘附性能大肠杆菌进行了研究通过流式细胞仪测量其荧光强度。在研究的这些ZnPc光敏剂中,具有四个正电荷的ZnPc共轭物(称为ZnPc-IR710)表现出最高的负载能力和最佳的荧光成像性能。在大肠杆菌的帮助下与ZnPc-IR710相比,大肠杆菌@ ZnPc-IR710对人乳腺癌MCF-7细胞具有明显增强的细胞毒性(肿瘤细胞的存活率分别为39%和57%)。 50nmol L -1)。此外,体内研究表明,大肠杆菌ZnPc-IR710显着抑制肿瘤生长,并在皮下小鼠4T1乳腺肿瘤模型中完全抑制肿瘤生长。这些结果证明了细菌引导的光动力疗法(PDT)在治疗实体瘤方面的巨大前景,并提供了通过利用肿瘤中的细菌载体来增强PDT的抗肿瘤功效的独特策略。

更新日期:2020-07-13
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