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
Background and Aims:Hepatitis B vaccination is the most cost effective way to prevent hepatitis B virus(HBV)infection.Hepatitis B vaccine(HepB)efficacy is usually assessed by an-ti-hepatitis B surface antigen(HBsAg)le...Background and Aims:Hepatitis B vaccination is the most cost effective way to prevent hepatitis B virus(HBV)infection.Hepatitis B vaccine(HepB)efficacy is usually assessed by an-ti-hepatitis B surface antigen(HBsAg)level,but there are few reports of humoral and cellular immune responses to HepB in children after neonatal vaccination.Methods:A group of 100 children with a history of primary hepatitis B immunization were included in this study to evaluate the efficacy of HepB.Blood samples were obtained from 80 children before,and 41 children after,a single HepB booster dose.Children with low anti-HBsAg(HBs)titers of<100 mIU/mL received a booster dose after giving their informed consent.Anti-HBsAg,T-cell re-sponse and percentage of B-cell subsets were assayed before and after the booster.Results:Of the 80 children,81.36%had positive T cell and anti-HBsAg responses at baseline.After the booster dose,the anti-HBsAg titer(p<0.0001),positive HBsAg-specific T-cell response(p=0.0036),and spot-form-ing cells(p=0.0003)increased significantly.Compared with pre-existing anti-HBsAg titer<10 mIU/mL,the anti-HBsAg(p=0.0005)and HBsAg-specific T-cell responses(p<0.0001)increased significantly in preexisting anti-HBsAg titer between 10 and 100 mIU/mL group.Change of the HBV-specific hu-moral response was the reverse of the T-cell response with age.Peripheral blood lymphocytes,B cells,and subset fre-quency decreased.Conclusions:HBV immunization protec-tion persisted at least 13 years after primary immunization because of the complementary presence of HBV-specific hu-moral antibodies and a T-cell immune response.One dose of a HepB booster induced protective anti-HBsAg and promoted an HBsAg-specific T-cell response.In HBV endemic regions,a HepB booster is recommended to children without anti-HBsAg because of effectiveness in HBV prevention.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This study was supported by the National Clinical Research Center for Child Health and Disorders General project(No.NCRCCHD-2019-GP-04)Central Government Guides Local Science and Technology Development projects-demonstration of Science and Technology Innovation projects,National Natural Science Foundation of China(No.81371876)Outstanding Youth Foundation of Children’s Hospital of Chongqing Medical University.
文摘Background and Aims:Hepatitis B vaccination is the most cost effective way to prevent hepatitis B virus(HBV)infection.Hepatitis B vaccine(HepB)efficacy is usually assessed by an-ti-hepatitis B surface antigen(HBsAg)level,but there are few reports of humoral and cellular immune responses to HepB in children after neonatal vaccination.Methods:A group of 100 children with a history of primary hepatitis B immunization were included in this study to evaluate the efficacy of HepB.Blood samples were obtained from 80 children before,and 41 children after,a single HepB booster dose.Children with low anti-HBsAg(HBs)titers of<100 mIU/mL received a booster dose after giving their informed consent.Anti-HBsAg,T-cell re-sponse and percentage of B-cell subsets were assayed before and after the booster.Results:Of the 80 children,81.36%had positive T cell and anti-HBsAg responses at baseline.After the booster dose,the anti-HBsAg titer(p<0.0001),positive HBsAg-specific T-cell response(p=0.0036),and spot-form-ing cells(p=0.0003)increased significantly.Compared with pre-existing anti-HBsAg titer<10 mIU/mL,the anti-HBsAg(p=0.0005)and HBsAg-specific T-cell responses(p<0.0001)increased significantly in preexisting anti-HBsAg titer between 10 and 100 mIU/mL group.Change of the HBV-specific hu-moral response was the reverse of the T-cell response with age.Peripheral blood lymphocytes,B cells,and subset fre-quency decreased.Conclusions:HBV immunization protec-tion persisted at least 13 years after primary immunization because of the complementary presence of HBV-specific hu-moral antibodies and a T-cell immune response.One dose of a HepB booster induced protective anti-HBsAg and promoted an HBsAg-specific T-cell response.In HBV endemic regions,a HepB booster is recommended to children without anti-HBsAg because of effectiveness in HBV prevention.
