BACKGROUND Hepatosplenic T-cell lymphoma(HSTCL)is a rare subtype of non-Hodgkin’s lymphoma,which has an aggressive clinical course and an extremely poor prognosis.Chidamide is a novel,orally active,benzamide-type his...BACKGROUND Hepatosplenic T-cell lymphoma(HSTCL)is a rare subtype of non-Hodgkin’s lymphoma,which has an aggressive clinical course and an extremely poor prognosis.Chidamide is a novel,orally active,benzamide-type histone deacetylase(HDAC)inhibitor that has been used for peripheral T-cell lymphoma(PTCL)treatment.However,to date,there has been no report of the treatment and effect of the HDAC inhibitor chidamide in HSTCL,which is a special subtype of PTCL.CASE SUMMARY A 45-year-old male patient was admitted with splenomegaly and slight bicytopenia.He was diagnosed with HSTCL via splenectomy.The patient was treated with fractionated cyclophosphamide,vincristine,doxorubicin,and dexamethasone alternating with high-dose methotrexate and cytarabine regiment as inductive therapy.Unfortunately,the disease progressed rapidly during chemotherapy before a suitable allogeneic gene transplant donor was found.The chidamide-combined chemotherapy regimen and single-drug oral maintenance regimen achieved complete remission,duration of response of 9 mo,and overall survival of 15 mo.CONCLUSION The novel agent chidamide can be used in HSTCL to achieve deep remission and improve the duration of response and overall survival.展开更多
The progression and metastasis of solid tumors strongly rely on the process of forming nascent blood vessels.However,using angiogenesis inhibitors alone does not meet the cancer treatment needs.Herein,we used the amph...The progression and metastasis of solid tumors strongly rely on the process of forming nascent blood vessels.However,using angiogenesis inhibitors alone does not meet the cancer treatment needs.Herein,we used the amphiphilic drug-drug conjugate(ADDC)strategy to fabricate a new drug conjugate with the combination of chemotherapeutic drug and antiangiogenesis drug together.With one-step esterification of hydrophilic floxuridine(FUDR)and hydrophobic pseudolaric acid B(PAB),the conjugate was synthesized.The amphiphilic property of FUDR-PAB conjugate induced the self-assembly to form nanoparticles in water.From further in vitro and in vivo experiments,this FUDR-PAB conjugate does not only have a high antitumor effect,but also shows efficient antianiogenesis property.These results offer a promising ADDC strategy for designing drugs with combination of chemotherapeutic drug and antiangiogenesis drug together.展开更多
A hyperbranched supramolecular polymer(HSP)is constructed based on the intermolecular inclusion complexation of bridged tris(permethyl-β-cyclodextrin)with Mn^(Ⅲ)-porphyrin bearing poly(ethylene glycol)(PEG)side chai...A hyperbranched supramolecular polymer(HSP)is constructed based on the intermolecular inclusion complexation of bridged tris(permethyl-β-cyclodextrin)with Mn^(Ⅲ)-porphyrin bearing poly(ethylene glycol)(PEG)side chains(Mn^(Ⅲ)-TPP),and characterized by UV/vis absorption spectroscopy,isothermal titration calorimetry(ITC),NMR,dynamic light scattering(DLS),atomic force microscopy(AFM)and transmission electron microscopy(TEM),respectively.The presence of permethyl-β-cyclodextrin can stabilize the low-valent Mn^(II)-TPP.In vitro cell experiment indicates that this HSP has no remarkable cellular toxicity against NIH 3T3 cells.In vitro MR imaging experiment indicates a slightly increased T_(1) relaxivity for this HSP compared to that for the linear supramolecular polymer.展开更多
Dual-modal surface enhanced Raman spectrum(SERS)-fluorescence polymer/metal hybrid complexes have been prepared for tracing drug release process in tumor cells. Firstly, the hyperbranched poly((S-(4-vinyl) benzyl S′-...Dual-modal surface enhanced Raman spectrum(SERS)-fluorescence polymer/metal hybrid complexes have been prepared for tracing drug release process in tumor cells. Firstly, the hyperbranched poly((S-(4-vinyl) benzyl S′-propyltrithiocarbonate)-co-(poly(ethylene glycol) methacrylate))(HPVBEG) was synthesized via the combination of reversible addition-fragmentation chain-transfer(RAFT) polymerization and self-condensing vinyl polymerization(SCVP). Subsequently, the anticancer drug doxorubicin(DOX) was linked to HPVBEG via pH sensitive Schiff base bonds to form HPVBEG-g-DOX conjugates.Through aminolysis reaction, HPVBEG-g-DOX was coordinated with gold nanoparticles(GNP), resulting in the formation of HPVBEG-g-DOX/GNP complexes. In neutral condition, the HPVBEG-g-DOX/GNP complexes were stable, and DOX was bound to the surface of GNPs. Therefore, the SERS of DOX could be observed, while the fluorescence of DOX was quenched by GNPs. Under an acidic environment, DOX was released from the surface of GNPs with breakage of Schiff base bonds.Thus, the SERS signal of DOX was gradually reduced. Correspondingly, the fluorescence signal of DOX was enhanced.Through dual-modal SERS-fluorescence technique, the DOX delivery and release process was traced in tumor cells. Moreover,the viability of MCF-7 cells incubated with HPVBEG-g-DOX/GNP complexes was investigated by Cell Counting Kit-8(CCK-8) assay. The experimental results showed that HPVBEG-g-DOX/GNP complexes had similar proliferation inhibition effect compared with free DOX. Definitely, the dual-modal SERS-fluorescence complexes for tracing drug delivery and release will have promising prospects on tumor diagnosis and therapy.展开更多
The influence of charges on cell membrane-incorporation behaviors of channel proteins remains incompletely understood due to the structural complexity of these proteins.In this study,the influence was investigated by ...The influence of charges on cell membrane-incorporation behaviors of channel proteins remains incompletely understood due to the structural complexity of these proteins.In this study,the influence was investigated by using asymmetric unimolecular artificial channels as simplified models.The study revealed a profound influence of terminal charge on interaction strength and kinetics.The negatively charged Ch^(-)exhibited significantly stronger interactions with lipid bilayers,demonstrated by an 83%membrane incorporation efficiency,compared to only 16%for the positively charged Ch^(+).Fluorescence correlation spectroscopy(FCS)and confocal microscopy confirmed that Ch^(-)rapidly inserts and redistributes within the membrane,while Ch^(+)shows slow,sporadic incorporation,attributed to electrostatic repulsion from positively charged lipid headgroups.Furthermore,the terminal charge critically dictated the channel's orientation within the bilayer.Using a fluorescence quenching assay,it was revealed that Ch^(-)predominantly adopts an outward-facing configuration(83%).In contrast,Ch^(+)favors an inward-facing orientation(only 19%outward).This orientation is driven by the initial anchoring of the hydrophobic end for Ch^(+),while for Ch^(-),electrostatic attraction facilitates a charged-end-first insertion.Single-particle tracking via total internal reflection fluorescence(TIRF)microscopy provided further kinetic insights:Ch^(-)aggregates adsorbed quickly and underwent dynamic redistribution,whereas Ch^(+)displayed rigid,immobilized binding once incorporated.This work unequivocally establishes molecular charge as a fundamental design parameter controlling the adsorption kinetics,binding stability,and ultimate orientation of artificial channels in lipid membranes.These findings provide essential principles for guiding the rational design of next-generation membrane-active therapeutic agents and biomimetic sensors.展开更多
基金a grant from the Department of Finance of Jilin Province,No.2018SCZWSZX-031.
文摘BACKGROUND Hepatosplenic T-cell lymphoma(HSTCL)is a rare subtype of non-Hodgkin’s lymphoma,which has an aggressive clinical course and an extremely poor prognosis.Chidamide is a novel,orally active,benzamide-type histone deacetylase(HDAC)inhibitor that has been used for peripheral T-cell lymphoma(PTCL)treatment.However,to date,there has been no report of the treatment and effect of the HDAC inhibitor chidamide in HSTCL,which is a special subtype of PTCL.CASE SUMMARY A 45-year-old male patient was admitted with splenomegaly and slight bicytopenia.He was diagnosed with HSTCL via splenectomy.The patient was treated with fractionated cyclophosphamide,vincristine,doxorubicin,and dexamethasone alternating with high-dose methotrexate and cytarabine regiment as inductive therapy.Unfortunately,the disease progressed rapidly during chemotherapy before a suitable allogeneic gene transplant donor was found.The chidamide-combined chemotherapy regimen and single-drug oral maintenance regimen achieved complete remission,duration of response of 9 mo,and overall survival of 15 mo.CONCLUSION The novel agent chidamide can be used in HSTCL to achieve deep remission and improve the duration of response and overall survival.
基金supported by the National Basic Research Program(2015CB931801)the National Natural Science Foundation of China(51690151,21504055)
文摘The progression and metastasis of solid tumors strongly rely on the process of forming nascent blood vessels.However,using angiogenesis inhibitors alone does not meet the cancer treatment needs.Herein,we used the amphiphilic drug-drug conjugate(ADDC)strategy to fabricate a new drug conjugate with the combination of chemotherapeutic drug and antiangiogenesis drug together.With one-step esterification of hydrophilic floxuridine(FUDR)and hydrophobic pseudolaric acid B(PAB),the conjugate was synthesized.The amphiphilic property of FUDR-PAB conjugate induced the self-assembly to form nanoparticles in water.From further in vitro and in vivo experiments,this FUDR-PAB conjugate does not only have a high antitumor effect,but also shows efficient antianiogenesis property.These results offer a promising ADDC strategy for designing drugs with combination of chemotherapeutic drug and antiangiogenesis drug together.
基金We thank the 973 Program(No.2011CB932500)the NNSFC(Nos.20932004,21372128 and 91227107)for financial support.
文摘A hyperbranched supramolecular polymer(HSP)is constructed based on the intermolecular inclusion complexation of bridged tris(permethyl-β-cyclodextrin)with Mn^(Ⅲ)-porphyrin bearing poly(ethylene glycol)(PEG)side chains(Mn^(Ⅲ)-TPP),and characterized by UV/vis absorption spectroscopy,isothermal titration calorimetry(ITC),NMR,dynamic light scattering(DLS),atomic force microscopy(AFM)and transmission electron microscopy(TEM),respectively.The presence of permethyl-β-cyclodextrin can stabilize the low-valent Mn^(II)-TPP.In vitro cell experiment indicates that this HSP has no remarkable cellular toxicity against NIH 3T3 cells.In vitro MR imaging experiment indicates a slightly increased T_(1) relaxivity for this HSP compared to that for the linear supramolecular polymer.
基金supported by the National Basic Research Program of China(2015CB931801)the National Natural Science Foundation of China(51473093)
文摘Dual-modal surface enhanced Raman spectrum(SERS)-fluorescence polymer/metal hybrid complexes have been prepared for tracing drug release process in tumor cells. Firstly, the hyperbranched poly((S-(4-vinyl) benzyl S′-propyltrithiocarbonate)-co-(poly(ethylene glycol) methacrylate))(HPVBEG) was synthesized via the combination of reversible addition-fragmentation chain-transfer(RAFT) polymerization and self-condensing vinyl polymerization(SCVP). Subsequently, the anticancer drug doxorubicin(DOX) was linked to HPVBEG via pH sensitive Schiff base bonds to form HPVBEG-g-DOX conjugates.Through aminolysis reaction, HPVBEG-g-DOX was coordinated with gold nanoparticles(GNP), resulting in the formation of HPVBEG-g-DOX/GNP complexes. In neutral condition, the HPVBEG-g-DOX/GNP complexes were stable, and DOX was bound to the surface of GNPs. Therefore, the SERS of DOX could be observed, while the fluorescence of DOX was quenched by GNPs. Under an acidic environment, DOX was released from the surface of GNPs with breakage of Schiff base bonds.Thus, the SERS signal of DOX was gradually reduced. Correspondingly, the fluorescence signal of DOX was enhanced.Through dual-modal SERS-fluorescence technique, the DOX delivery and release process was traced in tumor cells. Moreover,the viability of MCF-7 cells incubated with HPVBEG-g-DOX/GNP complexes was investigated by Cell Counting Kit-8(CCK-8) assay. The experimental results showed that HPVBEG-g-DOX/GNP complexes had similar proliferation inhibition effect compared with free DOX. Definitely, the dual-modal SERS-fluorescence complexes for tracing drug delivery and release will have promising prospects on tumor diagnosis and therapy.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFA1203401)the National Natural Science Foundation of China(NSFC+3 种基金Grant No.22171052)the Science and Technology Commission of Shanghai Municipality(STCSMGrant Nos.22JC140370022520712300).
文摘The influence of charges on cell membrane-incorporation behaviors of channel proteins remains incompletely understood due to the structural complexity of these proteins.In this study,the influence was investigated by using asymmetric unimolecular artificial channels as simplified models.The study revealed a profound influence of terminal charge on interaction strength and kinetics.The negatively charged Ch^(-)exhibited significantly stronger interactions with lipid bilayers,demonstrated by an 83%membrane incorporation efficiency,compared to only 16%for the positively charged Ch^(+).Fluorescence correlation spectroscopy(FCS)and confocal microscopy confirmed that Ch^(-)rapidly inserts and redistributes within the membrane,while Ch^(+)shows slow,sporadic incorporation,attributed to electrostatic repulsion from positively charged lipid headgroups.Furthermore,the terminal charge critically dictated the channel's orientation within the bilayer.Using a fluorescence quenching assay,it was revealed that Ch^(-)predominantly adopts an outward-facing configuration(83%).In contrast,Ch^(+)favors an inward-facing orientation(only 19%outward).This orientation is driven by the initial anchoring of the hydrophobic end for Ch^(+),while for Ch^(-),electrostatic attraction facilitates a charged-end-first insertion.Single-particle tracking via total internal reflection fluorescence(TIRF)microscopy provided further kinetic insights:Ch^(-)aggregates adsorbed quickly and underwent dynamic redistribution,whereas Ch^(+)displayed rigid,immobilized binding once incorporated.This work unequivocally establishes molecular charge as a fundamental design parameter controlling the adsorption kinetics,binding stability,and ultimate orientation of artificial channels in lipid membranes.These findings provide essential principles for guiding the rational design of next-generation membrane-active therapeutic agents and biomimetic sensors.
