Simple encapsulation of 3 nm gold nanoparticles in ordered mesoporous carbon with large pores of 17 nm and thick pore walls of 16 nm was achieved by a metal–ligand coordination assisted-selfassembly approach.Polystyr...Simple encapsulation of 3 nm gold nanoparticles in ordered mesoporous carbon with large pores of 17 nm and thick pore walls of 16 nm was achieved by a metal–ligand coordination assisted-selfassembly approach.Polystyrene-block-polyethylene-oxide(PS-b-PEO)diblock copolymer with a large molecular weight of the PS chain and mercaptopropyltrimethoxysilane were used as the template and the metal ligand,respectively.Small-angle X-ray scattering,X-ray diffraction,transmission electron microscopy,and X-ray photoelectron spectroscopy showed that monodispersed aggregation-free gold nanoparticles approximately 3 nm in size were partially embedded in the large open pore structure of the ordered mesoporous carbon.The strong coordination between the gold species and the mercapto groups and the thick porous walls increased the dispersion of the gold nanoparticles and essentially inhibited particle aggregation at 600℃.The gold nanoparticles in the ordered mesoporous carbon are active and stable in the reduction of nitroarenes involving bulky molecules using sodium borohydride as a reducing agent under ambient conditions(30℃)in water.The large interconnected pore structure facilitates the mass transfer of bulky molecules.展开更多
Background:Treatment with chimeric antigen receptor-T(CAR-T)cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia(R/R B-ALL),although the process of preparing...Background:Treatment with chimeric antigen receptor-T(CAR-T)cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia(R/R B-ALL),although the process of preparing for this therapy usually takes a long time.We have recently created CD19 Fast-CAR-T(F-CAR-T)cells,which can be produced within a single day.The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL.Methods:A multicenter,retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted.Overall,23 patients were administered with innovative CD19 F-CAR-T cells(F-CAR-T group),whereas 21 patients were given CD19 conventional CAR-T cells(C-CAR-T group).We compared the rates of complete remission(CR),minimal residual disease(MRD)-negative CR,leukemia-free survival(LFS),overall survival(OS),and the incidence of cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)between the two groups.Results:Compared with the C-CAR-T group,the F-CAR-T group had significantly higher CR and MRD-negative rates(95.7%and 91.3%,respectively;71.4%and 66.7%,respectively;P=0.036 and P=0.044).No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups:the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8%and 43.5%vs.38.1%and 23.8%(P=0.384 and P=0.216),while the 1-year and 2-year OS rates were 65.2%and 56.5%vs.52.4%and 47.6%(P=0.395 and P=0.540).Additionally,among CR patients who underwent allogeneic hematopoietic stem cell transplantation(allo-HSCT)following CAR-T-cell therapy,there were no significant differences in the 1-year or 2-year LFS or OS rates:57.1%and 50.0%vs.47.8%and 34.8%(P=0.506 and P=0.356),64.3%and 57.1%vs.65.2%and 56.5%(P=0.985 and P=0.883),respectively.The incidence of CRS was greater in the F-CAR-T group(91.3%)than in the C-CAR-T group(66.7%)(P=0.044).The incidence of ICANS was also greater in the F-CAR-T group(30.4%)than in the C-CAR-T group(9.5%)(P=0.085),but no treatment-related deaths occurred in the two groups.Conclusion:Compared with C-CAR-T-cell therapy,F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS.Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.展开更多
基金supported by the National Natural Science Foun-dation of China(22025204,92034301,21773156,and 51932005)the Shanghai Sci.&Tech.and Edu.Committee(19070502700)the Innovation Program of the Shanghai Municipal Education Com-mission(2021-01-07-00-02-E00119).
文摘Simple encapsulation of 3 nm gold nanoparticles in ordered mesoporous carbon with large pores of 17 nm and thick pore walls of 16 nm was achieved by a metal–ligand coordination assisted-selfassembly approach.Polystyrene-block-polyethylene-oxide(PS-b-PEO)diblock copolymer with a large molecular weight of the PS chain and mercaptopropyltrimethoxysilane were used as the template and the metal ligand,respectively.Small-angle X-ray scattering,X-ray diffraction,transmission electron microscopy,and X-ray photoelectron spectroscopy showed that monodispersed aggregation-free gold nanoparticles approximately 3 nm in size were partially embedded in the large open pore structure of the ordered mesoporous carbon.The strong coordination between the gold species and the mercapto groups and the thick porous walls increased the dispersion of the gold nanoparticles and essentially inhibited particle aggregation at 600℃.The gold nanoparticles in the ordered mesoporous carbon are active and stable in the reduction of nitroarenes involving bulky molecules using sodium borohydride as a reducing agent under ambient conditions(30℃)in water.The large interconnected pore structure facilitates the mass transfer of bulky molecules.
基金This work was supported by grants the National Natural Science Foundation of China(Nos.82341201 and 82370181)the National Key R&D Program of China(Nos.2022YFA1103300 and 2022YFA1103304)+1 种基金the Chongqing Science and Health Joint Medical Research Project(No.2024QNXM025)the Special Project for Talent Construction in Xinqiao Hospital of Army Medical University(No.2022XKRC001)
文摘Background:Treatment with chimeric antigen receptor-T(CAR-T)cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia(R/R B-ALL),although the process of preparing for this therapy usually takes a long time.We have recently created CD19 Fast-CAR-T(F-CAR-T)cells,which can be produced within a single day.The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL.Methods:A multicenter,retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted.Overall,23 patients were administered with innovative CD19 F-CAR-T cells(F-CAR-T group),whereas 21 patients were given CD19 conventional CAR-T cells(C-CAR-T group).We compared the rates of complete remission(CR),minimal residual disease(MRD)-negative CR,leukemia-free survival(LFS),overall survival(OS),and the incidence of cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)between the two groups.Results:Compared with the C-CAR-T group,the F-CAR-T group had significantly higher CR and MRD-negative rates(95.7%and 91.3%,respectively;71.4%and 66.7%,respectively;P=0.036 and P=0.044).No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups:the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8%and 43.5%vs.38.1%and 23.8%(P=0.384 and P=0.216),while the 1-year and 2-year OS rates were 65.2%and 56.5%vs.52.4%and 47.6%(P=0.395 and P=0.540).Additionally,among CR patients who underwent allogeneic hematopoietic stem cell transplantation(allo-HSCT)following CAR-T-cell therapy,there were no significant differences in the 1-year or 2-year LFS or OS rates:57.1%and 50.0%vs.47.8%and 34.8%(P=0.506 and P=0.356),64.3%and 57.1%vs.65.2%and 56.5%(P=0.985 and P=0.883),respectively.The incidence of CRS was greater in the F-CAR-T group(91.3%)than in the C-CAR-T group(66.7%)(P=0.044).The incidence of ICANS was also greater in the F-CAR-T group(30.4%)than in the C-CAR-T group(9.5%)(P=0.085),but no treatment-related deaths occurred in the two groups.Conclusion:Compared with C-CAR-T-cell therapy,F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS.Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.