To meet the high requirements of biomedical applications in antimicrobial agents, it is crucial to explore efficient nanoantimicrobialagents with no resistance and good biocompatibility for treating infected wounds. I...To meet the high requirements of biomedical applications in antimicrobial agents, it is crucial to explore efficient nanoantimicrobialagents with no resistance and good biocompatibility for treating infected wounds. In this study, compositenano-antibiotic TPA-Py@AuNCs⊂BSA nanoparticles (TAB NPs) are prepared using hollow mesoporous Au nanocages (AuNCs)loaded with a photosensitizer (namely TPA-Py) with D-π-A structure showing aggregation-induced emission properties. WhenTPA-Py is encapsulated in the cavity of AuNCs, its fluorescence is suppressed. In the presence of photothermal induction, TPA-Pycan be released from the AuNCs, allowing for the restoration of fluorescence illumination and the specific imaging of Grampositivebacteria. TAB NPs demonstrate outstanding antimicrobial activity against a variety of bacteria, and this multimodalantimicrobial property does not lead to the development of bacterial resistance. In vitro experiments show that TAB NPs couldeliminate bacteria and ablate bacterial biofilm. In vivo experiments show that the synergistic antimicrobial effect of TAB NPs has asignificant positive impact on the treatment of infectedwounds, including rapid antibacterial action, promotion of M2 macrophagepolarization, and enhancement of chronic wound healing. This study provides an effective strategy for developing wide-spectrumnano-antibiotics for the ablation of bacterial biofilms and the treatment of infected wounds.展开更多
Increasing numbers of targeted drugs are used in hormone receptor(HR)-positive metastatic breast cancer(MBC)to overcome or delay resistance to endocrine therapy.This study will systemically review the progress made in...Increasing numbers of targeted drugs are used in hormone receptor(HR)-positive metastatic breast cancer(MBC)to overcome or delay resistance to endocrine therapy.This study will systemically review the progress made in endocrine therapy combined with targeted therapy in the treatment of HR-positive MBC.From the“AI(aromatase inhibitor)era”represented by aromatase inhibitors,we have gradually entered the“post-AI era”represented by fulvestrant.Under the guidance of research on the molecular mechanism of endocrine therapy resistance,the“combination of endocrine therapy and targeted therapy”era is approaching.The development of drugs that target endocrine therapy resistance has concentrated on cyclin-dependent kinase 4/6 inhibitors,histone deacetylase inhibitors,and inhibitors of drug targets in the phosphatidylinositol 3 kinase-protein kinase B-mammalian target of rapamycin(PI3K-AKT-mTOR)pathway,providing new strategies for HR-positive MBC.Exploring biomarkers to guide the more precise use of targeted drugs in endocrine therapy for MBC is the focus of current and future research.展开更多
基金The authors gratefully acknowledge the Research Foundation of Education Department of Shaanxi Province(23JK0282)fund of Rising Stars of Shaanxi Province(2021KJXX-48)+2 种基金the National Natural Science Foundation of China(52173152 and 21805002)the Scientific and Technological Innovation Team of Shaanxi Province(2022TD-36)the Natural Science Basic Research Program of Shaanxi Province(2024JC-YBQN-0107,2024JC-YBMS-114,and 2024JC-YBQN-0782).
文摘To meet the high requirements of biomedical applications in antimicrobial agents, it is crucial to explore efficient nanoantimicrobialagents with no resistance and good biocompatibility for treating infected wounds. In this study, compositenano-antibiotic TPA-Py@AuNCs⊂BSA nanoparticles (TAB NPs) are prepared using hollow mesoporous Au nanocages (AuNCs)loaded with a photosensitizer (namely TPA-Py) with D-π-A structure showing aggregation-induced emission properties. WhenTPA-Py is encapsulated in the cavity of AuNCs, its fluorescence is suppressed. In the presence of photothermal induction, TPA-Pycan be released from the AuNCs, allowing for the restoration of fluorescence illumination and the specific imaging of Grampositivebacteria. TAB NPs demonstrate outstanding antimicrobial activity against a variety of bacteria, and this multimodalantimicrobial property does not lead to the development of bacterial resistance. In vitro experiments show that TAB NPs couldeliminate bacteria and ablate bacterial biofilm. In vivo experiments show that the synergistic antimicrobial effect of TAB NPs has asignificant positive impact on the treatment of infectedwounds, including rapid antibacterial action, promotion of M2 macrophagepolarization, and enhancement of chronic wound healing. This study provides an effective strategy for developing wide-spectrumnano-antibiotics for the ablation of bacterial biofilms and the treatment of infected wounds.
基金a grant from the Capital Clinical Feature Project of Beijing(No.Z181100001718215).
文摘Increasing numbers of targeted drugs are used in hormone receptor(HR)-positive metastatic breast cancer(MBC)to overcome or delay resistance to endocrine therapy.This study will systemically review the progress made in endocrine therapy combined with targeted therapy in the treatment of HR-positive MBC.From the“AI(aromatase inhibitor)era”represented by aromatase inhibitors,we have gradually entered the“post-AI era”represented by fulvestrant.Under the guidance of research on the molecular mechanism of endocrine therapy resistance,the“combination of endocrine therapy and targeted therapy”era is approaching.The development of drugs that target endocrine therapy resistance has concentrated on cyclin-dependent kinase 4/6 inhibitors,histone deacetylase inhibitors,and inhibitors of drug targets in the phosphatidylinositol 3 kinase-protein kinase B-mammalian target of rapamycin(PI3K-AKT-mTOR)pathway,providing new strategies for HR-positive MBC.Exploring biomarkers to guide the more precise use of targeted drugs in endocrine therapy for MBC is the focus of current and future research.
