In this single-arm,phase 2 study,we explored the efficacy and safety of hepatic arterial infusion chemotherapy(HAIC)combined with anlotinib and TQB2450(an anti-PD-L1 antibody)as a postoperative adjuvant treatment in p...In this single-arm,phase 2 study,we explored the efficacy and safety of hepatic arterial infusion chemotherapy(HAIC)combined with anlotinib and TQB2450(an anti-PD-L1 antibody)as a postoperative adjuvant treatment in patients at high risk of hepatocellular carcinoma(HCC)recurrence.Patients with high-risk recurrence of HCC were treated with HAIC,anlotinib(4 or 8 cycles),and TQB2450 after curative surgery.The primary endpoint was disease-free survival(DFS),and the secondary endpoints included overall survival(OS)and safety.77 patients who met the inclusion criteria were enrolled:38 in the 4-cycle cohort and 39 in the 8-cycle cohort.As of the data cutoff on June 24,2024,the median follow-up period was 21.19 months(95%confidence interval[CI],20.49–21.89).The median DFS and OS of all patients were not reached.1-year and 2-year DFS rates were 84.4%and 65.8%,respectively,while 1-year and 2-year OS rates were 96.1%and 89.8%,respectively.No significant differences in DFS and OS were observed in patients treated with 4 or 8 cycles of anlotinib.The incidence of grade 3/4 adverse events(AEs)was 28.6%.Postoperative adjuvant HAIC combined with anlotinib and TQB2450 demonstrated encouraging clinical benefits in reducing recurrence with manageable toxicities in patients at high risk of HCC recurrence.4-cycle anlotinib combined with HAIC and TQB2450 is recommended as an adjuvant treatment for further investigation.展开更多
miRNAs are important regulators of gene expression and play key roles in the development of cancer, including osteosarcoma. During the development of osteosarcoma, the expression of miR-22 is significantly downregulat...miRNAs are important regulators of gene expression and play key roles in the development of cancer, including osteosarcoma. During the development of osteosarcoma, the expression of miR-22 is significantly downregulated, making miR-22 as a promising therapeutic target against osteosarcoma. To design and fabricate efficient delivery carriers of miR-22 into osteosarcoma cells, a hydroxyl-rich reduction-responsive cationic polymeric nanoparticle, TGIC-CA (TC), was developed in this work, which also enhanced the therapeutic effects of Volasertib on osteosarcoma. TC was prepared by the ring-opening reaction between amino and epoxy groups by one-pot method, which had the good complexing ability with nucleic acids, reduction-responsive degradability and gene transfection performance. TC/miR-22 combined with volasertib could inhibit proliferation, migration and promote apoptosis of osteosarcoma cells in vitro. The anti-tumor mechanisms were revealed as TC/ miR-22 and volasertib could inhibit the PI3K/Akt signaling pathway synergistically. Furthermore, this strategy showed outstanding tumor suppression performance in animal models of orthotopic osteosarcoma, especially in patient-derived chemo-resistant and chemo-intolerant patient-derived xenograft (PDX) models, which reduced the risk of tumor lung metastasis and overcame drug resistance. Therefore, it has great potential for efficient treatment of metastasis and drug resistance of osteosarcoma by the strategy of localized, sustained delivery of miR-22 using the cationic nanocarriers combined with non-traditional chemotherapy drugs.展开更多
High levels of cell-free DNA(cfDNA)induce psoriasis.Currently,the treatment of psoriasis has the disadvantages of penetration difficulty,suppression of normal immunity,and skin irritation.In this study,biguanide chito...High levels of cell-free DNA(cfDNA)induce psoriasis.Currently,the treatment of psoriasis has the disadvantages of penetration difficulty,suppression of normal immunity,and skin irritation.In this study,biguanide chitosan microneedles(BGC-MNs)were prepared to treat psoriasis by removing cfDNA from the dermis through the skin barrier.The effects of chitosan with different bisguanidine contents on DNA-binding capacity,biocompatibility,and inflammation inhibition were compared,revealing that chitosan containing 20%bisguanidine(BGC2)was found to have the best overall performance.In vitro,BGC2 effectively cleared cfDNA and inhibited the production of inflammatory factors.BGC-MN made from BGC2 had good mechanical and solubility properties.In vivo,BGC-MNs cleared cfDNA,reduced the level of inflammatory factors in the dermis,and exerted a good therapeutic effect on mice with psoriasis.These results suggested that BGC-MNs provided a new approach to treating psoriasis in terms of scavenging cfDNA and exerting anti-inflammatory effects.展开更多
The abuse of antibiotics in treating microbial infections has led to the emergence and prevalence of drugresistant bacteria.Thus,the development of novel antibacterial materials is attracting increasing attention.Here...The abuse of antibiotics in treating microbial infections has led to the emergence and prevalence of drugresistant bacteria.Thus,the development of novel antibacterial materials is attracting increasing attention.Here,a series of flexible electrostatic hydrogels with excellent antibacterial ability were constructed using a mixture of nitric oxide(NO)-releasing nitrated chitosan(CSNO)and mesotetra(4-carboxyphenyl)porphine(TCPP)with salmon sperm DNA(ssDNA)solution.When cultured with gram-negative bacteria under solar simulator irradiation,TCPP-CSNO_(m)ssDNA_(n) hydrogels released reactive oxygen species(ROS)and NO to produce peroxynitrite ions(ONOO^(−)).ONOO−is efficient at killing bacteria,thereby improving the antimicrobial ability of photodynamic therapy against gram-negative bacteria.The hydrogels exhibited powerful antibacterial activity in vivo when used to treat skin infections caused by drugresistant bacteria,making them a promising candidate for clinical applications.A string of antibacterial hydrogels that release ROS and NO synergistically can bring new possibilities for effectively killing drug-resistant bacteria and be of great value in anti-infection wound dressings and other applications.展开更多
Chemiluminescence(CL)is an emission phenomenon induced by chemical reaction.Different from the photoluminescence,CL is free from external excitation source,which is expected to show great advantages such as higher sig...Chemiluminescence(CL)is an emission phenomenon induced by chemical reaction.Different from the photoluminescence,CL is free from external excitation source,which is expected to show great advantages such as higher signal-to-background ratio(SBR)in bioimaging,and deeper tissue penetration in photodynamic therapy(PDT).This review introduces the theoretical aspects of CL mechanism,such as classification,energy consideration and chemiexcited/photoexcited states.Application of CL in bioimaging is highlighted.In particular,the approaches to modulate the brightness and the wavelength of CL are summarized,which are two fundamental parameters in bioimaging.Finally,the application of CL in PDT is introduced.The potential challenges and perspectives of CL in bioimaging and therapy are also discussed.展开更多
The escalating issue of lung infections induced by multi-drug resistant(MDR)bacteria is threatening human health.Thus,the development of efficient drug delivery systems is essential to eliminate MDR bacterial lung inf...The escalating issue of lung infections induced by multi-drug resistant(MDR)bacteria is threatening human health.Thus,the development of efficient drug delivery systems is essential to eliminate MDR bacterial lung infections effectively.Herein,we designed inhalable drug-loaded nano-assemblies by the electrostatic interaction between negatively charged sodium alginate and a positively charged antibacterial polymer,quaternized polyethyleneimine(QPEI-C_(6)),as well as a kind of typical antibiotic for therapy of lung infection,azithromycin(AZT).By adjusting the feed ratios,we optimized the size of the nano-assembly to approximately 200 nm(STQ_(12)),which was beneficial for penetration through the mucus layer and biofilm.In the slightly acidic environment of the infected site,the nano-assembly could dissemble responsively and release AZT and QPEI-C_(6).Because of the combined bactericidal effect,STQ_(12)exhibited high bactericidal efficiency against MDR bacteria.In animal experiments,STQ_(12)showed notable efficacy against MDR bacterial lung infection.Gene transcriptomic results showed that the main effects of STQ_(12)against bacteria were through influencing the bacterial cell components and metabolic processes,and affecting their growth and reproduction.This work provides a promising strategy to treat MDR bacterium-induced lower respiratory tract infections.展开更多
基金supported by the National Natural Science Foundation of China(82472956 and M-0334)the China Postdoctoral Science Foundation(BX20240082 and 2024M750536)+2 种基金the Shanghai Rising Star Program Sailing Project(24YF2705600 and 24YF2738200)the Shanghai Xuhui District Hospital Local Cooperation Project(23XHYD-20)the Shanghai Xuhui District Health Commission’s Joint Research Project on Key Diseases(XHLHGG202103).
文摘In this single-arm,phase 2 study,we explored the efficacy and safety of hepatic arterial infusion chemotherapy(HAIC)combined with anlotinib and TQB2450(an anti-PD-L1 antibody)as a postoperative adjuvant treatment in patients at high risk of hepatocellular carcinoma(HCC)recurrence.Patients with high-risk recurrence of HCC were treated with HAIC,anlotinib(4 or 8 cycles),and TQB2450 after curative surgery.The primary endpoint was disease-free survival(DFS),and the secondary endpoints included overall survival(OS)and safety.77 patients who met the inclusion criteria were enrolled:38 in the 4-cycle cohort and 39 in the 8-cycle cohort.As of the data cutoff on June 24,2024,the median follow-up period was 21.19 months(95%confidence interval[CI],20.49–21.89).The median DFS and OS of all patients were not reached.1-year and 2-year DFS rates were 84.4%and 65.8%,respectively,while 1-year and 2-year OS rates were 96.1%and 89.8%,respectively.No significant differences in DFS and OS were observed in patients treated with 4 or 8 cycles of anlotinib.The incidence of grade 3/4 adverse events(AEs)was 28.6%.Postoperative adjuvant HAIC combined with anlotinib and TQB2450 demonstrated encouraging clinical benefits in reducing recurrence with manageable toxicities in patients at high risk of HCC recurrence.4-cycle anlotinib combined with HAIC and TQB2450 is recommended as an adjuvant treatment for further investigation.
基金supported by National Natural Science Foundation of China(Grant Nos.51973021,52221006,52173275,51932002 and 51903013)Beijing Municipal Health Commission(BJRITO-RDP-2023,PXM 2020_026275_000002 and BMHC-2021-6)+2 种基金National Key Research and Development Program(Grant No.2021YFC2400500)Beijing Jishuitan Hospital Nova Program(Grant Nos.XKXX202115 and XKXX202114)Beijing Outstanding Young Scientist Program(Grant No.BJJWZYJH01201910010024).
文摘miRNAs are important regulators of gene expression and play key roles in the development of cancer, including osteosarcoma. During the development of osteosarcoma, the expression of miR-22 is significantly downregulated, making miR-22 as a promising therapeutic target against osteosarcoma. To design and fabricate efficient delivery carriers of miR-22 into osteosarcoma cells, a hydroxyl-rich reduction-responsive cationic polymeric nanoparticle, TGIC-CA (TC), was developed in this work, which also enhanced the therapeutic effects of Volasertib on osteosarcoma. TC was prepared by the ring-opening reaction between amino and epoxy groups by one-pot method, which had the good complexing ability with nucleic acids, reduction-responsive degradability and gene transfection performance. TC/miR-22 combined with volasertib could inhibit proliferation, migration and promote apoptosis of osteosarcoma cells in vitro. The anti-tumor mechanisms were revealed as TC/ miR-22 and volasertib could inhibit the PI3K/Akt signaling pathway synergistically. Furthermore, this strategy showed outstanding tumor suppression performance in animal models of orthotopic osteosarcoma, especially in patient-derived chemo-resistant and chemo-intolerant patient-derived xenograft (PDX) models, which reduced the risk of tumor lung metastasis and overcame drug resistance. Therefore, it has great potential for efficient treatment of metastasis and drug resistance of osteosarcoma by the strategy of localized, sustained delivery of miR-22 using the cationic nanocarriers combined with non-traditional chemotherapy drugs.
基金supported by National Key R&D Program of China(Grant number 2021YFB3800900)National Natural Science Foundation of China(Grant numbers 52073013,22122501,52221006 and 52161145410)+1 种基金Beijing Outstanding Young Scientist Program(No.BJJWZYJH01201910010024)approved by the Ethical Committee of Chinese Academy of Medical Sciences(CAMS).
文摘High levels of cell-free DNA(cfDNA)induce psoriasis.Currently,the treatment of psoriasis has the disadvantages of penetration difficulty,suppression of normal immunity,and skin irritation.In this study,biguanide chitosan microneedles(BGC-MNs)were prepared to treat psoriasis by removing cfDNA from the dermis through the skin barrier.The effects of chitosan with different bisguanidine contents on DNA-binding capacity,biocompatibility,and inflammation inhibition were compared,revealing that chitosan containing 20%bisguanidine(BGC2)was found to have the best overall performance.In vitro,BGC2 effectively cleared cfDNA and inhibited the production of inflammatory factors.BGC-MN made from BGC2 had good mechanical and solubility properties.In vivo,BGC-MNs cleared cfDNA,reduced the level of inflammatory factors in the dermis,and exerted a good therapeutic effect on mice with psoriasis.These results suggested that BGC-MNs provided a new approach to treating psoriasis in terms of scavenging cfDNA and exerting anti-inflammatory effects.
基金supported by the National Key R&D Program of China(2021YFB3800900)the National Natural Science Foundation of China(22122501,21875014 and 52073013)Beijing Outstanding Young Scientist Program(BJJWZYJH01201910010024)。
文摘The abuse of antibiotics in treating microbial infections has led to the emergence and prevalence of drugresistant bacteria.Thus,the development of novel antibacterial materials is attracting increasing attention.Here,a series of flexible electrostatic hydrogels with excellent antibacterial ability were constructed using a mixture of nitric oxide(NO)-releasing nitrated chitosan(CSNO)and mesotetra(4-carboxyphenyl)porphine(TCPP)with salmon sperm DNA(ssDNA)solution.When cultured with gram-negative bacteria under solar simulator irradiation,TCPP-CSNO_(m)ssDNA_(n) hydrogels released reactive oxygen species(ROS)and NO to produce peroxynitrite ions(ONOO^(−)).ONOO−is efficient at killing bacteria,thereby improving the antimicrobial ability of photodynamic therapy against gram-negative bacteria.The hydrogels exhibited powerful antibacterial activity in vivo when used to treat skin infections caused by drugresistant bacteria,making them a promising candidate for clinical applications.A string of antibacterial hydrogels that release ROS and NO synergistically can bring new possibilities for effectively killing drug-resistant bacteria and be of great value in anti-infection wound dressings and other applications.
文摘Chemiluminescence(CL)is an emission phenomenon induced by chemical reaction.Different from the photoluminescence,CL is free from external excitation source,which is expected to show great advantages such as higher signal-to-background ratio(SBR)in bioimaging,and deeper tissue penetration in photodynamic therapy(PDT).This review introduces the theoretical aspects of CL mechanism,such as classification,energy consideration and chemiexcited/photoexcited states.Application of CL in bioimaging is highlighted.In particular,the approaches to modulate the brightness and the wavelength of CL are summarized,which are two fundamental parameters in bioimaging.Finally,the application of CL in PDT is introduced.The potential challenges and perspectives of CL in bioimaging and therapy are also discussed.
基金Beijing Outstanding Young Scientist Program,Grant/Award Number:BJJWZYJH01201910010024National Natural Science Foundation of China,Grant/Award Numbers:52073024,52122304,52221006,52293382Beijing Municipal Science and Technology Project,Grant/Award Number:Z191100006619099。
文摘The escalating issue of lung infections induced by multi-drug resistant(MDR)bacteria is threatening human health.Thus,the development of efficient drug delivery systems is essential to eliminate MDR bacterial lung infections effectively.Herein,we designed inhalable drug-loaded nano-assemblies by the electrostatic interaction between negatively charged sodium alginate and a positively charged antibacterial polymer,quaternized polyethyleneimine(QPEI-C_(6)),as well as a kind of typical antibiotic for therapy of lung infection,azithromycin(AZT).By adjusting the feed ratios,we optimized the size of the nano-assembly to approximately 200 nm(STQ_(12)),which was beneficial for penetration through the mucus layer and biofilm.In the slightly acidic environment of the infected site,the nano-assembly could dissemble responsively and release AZT and QPEI-C_(6).Because of the combined bactericidal effect,STQ_(12)exhibited high bactericidal efficiency against MDR bacteria.In animal experiments,STQ_(12)showed notable efficacy against MDR bacterial lung infection.Gene transcriptomic results showed that the main effects of STQ_(12)against bacteria were through influencing the bacterial cell components and metabolic processes,and affecting their growth and reproduction.This work provides a promising strategy to treat MDR bacterium-induced lower respiratory tract infections.
