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...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.展开更多
Hypoxia is a hallmark of solid tumors,and it significantly impairs the overall anticancer efficacy,particularly photodynamic therapy(PDT).Herein,a catalase-like nanovesicle with near-infrared light-responsiveness,that...Hypoxia is a hallmark of solid tumors,and it significantly impairs the overall anticancer efficacy,particularly photodynamic therapy(PDT).Herein,a catalase-like nanovesicle with near-infrared light-responsiveness,that is,platinum/gold nanoshell encapsulated chlorin e6(Ce6)/resveratrol(Res)liposome(Pt@Au-Ce6/Res-Lip),was developed to surmount this intractable issue.The Pt@Au-Ce6/Res-Lip can decompose overexpressed H_(2)O_(2)in tumor microenvironment to produce vast amounts of O_(2)for further enhancement of the PDT.Under the 808 nm laser irradiation,the Au nanoshells induced hyperthermia at the lesion site to ablate tumor cells,simultaneously inducing the controlled release of photosensitizer Ce6 and chemotherapeutic agent Res.Moreover,stimulated by 660 nm laser,numerous reactive oxygen species were formed to induce apoptosis and necrosis of tumor cells.With the cascade of trimodal therapeutic modality options(chemotherapy,photothermal therapy,and PDT),the Pt@Au-Ce6/Res-Lip showed ultrahigh tumor inhabitation rate in in vitro and in vivo studies,signifying that the Pt@AuCe6/Res-Lip nanovesicle is a promising candidate for effective cancer therapy.展开更多
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)。
文摘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.
基金the National Natural Science Foundation(21776238,21476190,and 31801198)Hebei province Natural fund key projects(B2019203479)。
文摘Hypoxia is a hallmark of solid tumors,and it significantly impairs the overall anticancer efficacy,particularly photodynamic therapy(PDT).Herein,a catalase-like nanovesicle with near-infrared light-responsiveness,that is,platinum/gold nanoshell encapsulated chlorin e6(Ce6)/resveratrol(Res)liposome(Pt@Au-Ce6/Res-Lip),was developed to surmount this intractable issue.The Pt@Au-Ce6/Res-Lip can decompose overexpressed H_(2)O_(2)in tumor microenvironment to produce vast amounts of O_(2)for further enhancement of the PDT.Under the 808 nm laser irradiation,the Au nanoshells induced hyperthermia at the lesion site to ablate tumor cells,simultaneously inducing the controlled release of photosensitizer Ce6 and chemotherapeutic agent Res.Moreover,stimulated by 660 nm laser,numerous reactive oxygen species were formed to induce apoptosis and necrosis of tumor cells.With the cascade of trimodal therapeutic modality options(chemotherapy,photothermal therapy,and PDT),the Pt@Au-Ce6/Res-Lip showed ultrahigh tumor inhabitation rate in in vitro and in vivo studies,signifying that the Pt@AuCe6/Res-Lip nanovesicle is a promising candidate for effective cancer therapy.
