Carbon monoxide(CO)gas therapy,a novel anti-tumor technique based on the cytotoxicity from the CO released in situ,has become one of the hot topics in cancer treatment.Since the technique is oxygenindependent,it displ...Carbon monoxide(CO)gas therapy,a novel anti-tumor technique based on the cytotoxicity from the CO released in situ,has become one of the hot topics in cancer treatment.Since the technique is oxygenindependent,it displays promising therapeutic effect for hypoxic tumor where traditional photodynamic therapy shows limited efficacy and insufficient penetration depth.To fully address these limitations of PDT,we propose a synergetic sonodynamic-CO gas releasing strategy for the therapy of hypoxic tumor.In this work,two rhenium(Ⅰ)tricarbonyl complexes with different substituted ligands are investigated for US-triggered ROS generation and CO release.Our results indicated that the electron-donating NMe2-substituted complex(Re-NMe2)exhibits stronger luminescence intensity and generates more singlet oxygen(1O2)than the electron-withdrawing NO2-substituted complex(Re-NO2).In addition,Re-NMe2displays release of CO triggered by US,thus showing high sono-cytotoxicity to tumor cells in-vitro and in-vivo.The strong ROS-generating capability combined with rapid CO-releasing feature from Re-NMe2has made it a powerful tool for the efficient treatment of hypoxic tumor.展开更多
Bacterial infection is the leading cause of many severe inflammation diseases. The development of novel and effective therapeutic approaches to counter bacterial infections, especially for drug-resistant bacteria, is ...Bacterial infection is the leading cause of many severe inflammation diseases. The development of novel and effective therapeutic approaches to counter bacterial infections, especially for drug-resistant bacteria, is essential. Herein, we have successfully developed an ultrasound-active tricarbonyl rhenium(Ⅰ) complex with tetraphenylethylene(TPE) modification(RePyTPE) for CO gas therapy and sonodynamic therapy of bacterial infections. RePy-TPE produced reactive oxygen species and released CO under ultrasound irradiation. In addition, RePy-TPE showed aggregation-induced emission in water due to the introduction of TPE, which enhanced the yield of ^(1)O_(2) generation in a biological aqueous solution. The produced ^(1)O_(2) and released CO killed mycobacterium smegmatis(M. smegmatis) and Escherichia coli(E. coli), as shown by bacterial membrane damage and biofilm elimination. Furthermore, ultrasound-active RePy-TPE perturbed the purine metabolism of the bacteria, which disturbed the biosynthesis of DNA and energy metabolism, eventually reducing the vitality of bacteria. This article provides a novel strategy for the development of ultrasound-active metal-based antibiotics.展开更多
基金the financial support of the National Natural Science Foundation of China(NSFC,No.22077085)the Science and Technology Foundation of Shenzhen(Nos.JCYJ20210324095200002,JCYJ20190808153209537)。
文摘Carbon monoxide(CO)gas therapy,a novel anti-tumor technique based on the cytotoxicity from the CO released in situ,has become one of the hot topics in cancer treatment.Since the technique is oxygenindependent,it displays promising therapeutic effect for hypoxic tumor where traditional photodynamic therapy shows limited efficacy and insufficient penetration depth.To fully address these limitations of PDT,we propose a synergetic sonodynamic-CO gas releasing strategy for the therapy of hypoxic tumor.In this work,two rhenium(Ⅰ)tricarbonyl complexes with different substituted ligands are investigated for US-triggered ROS generation and CO release.Our results indicated that the electron-donating NMe2-substituted complex(Re-NMe2)exhibits stronger luminescence intensity and generates more singlet oxygen(1O2)than the electron-withdrawing NO2-substituted complex(Re-NO2).In addition,Re-NMe2displays release of CO triggered by US,thus showing high sono-cytotoxicity to tumor cells in-vitro and in-vivo.The strong ROS-generating capability combined with rapid CO-releasing feature from Re-NMe2has made it a powerful tool for the efficient treatment of hypoxic tumor.
基金supported by the Natural Science Foundation of Guangdong Province (2023B1515020060, 2021B1515020050)the Science and Technology Foundation of Shenzhen (RCYX20221008092906021, JCYJ20210324095200002, JCYJ20220531103405012)the National Natural Science Foundation of China (22077085, 22177078, 22277153)。
文摘Bacterial infection is the leading cause of many severe inflammation diseases. The development of novel and effective therapeutic approaches to counter bacterial infections, especially for drug-resistant bacteria, is essential. Herein, we have successfully developed an ultrasound-active tricarbonyl rhenium(Ⅰ) complex with tetraphenylethylene(TPE) modification(RePyTPE) for CO gas therapy and sonodynamic therapy of bacterial infections. RePy-TPE produced reactive oxygen species and released CO under ultrasound irradiation. In addition, RePy-TPE showed aggregation-induced emission in water due to the introduction of TPE, which enhanced the yield of ^(1)O_(2) generation in a biological aqueous solution. The produced ^(1)O_(2) and released CO killed mycobacterium smegmatis(M. smegmatis) and Escherichia coli(E. coli), as shown by bacterial membrane damage and biofilm elimination. Furthermore, ultrasound-active RePy-TPE perturbed the purine metabolism of the bacteria, which disturbed the biosynthesis of DNA and energy metabolism, eventually reducing the vitality of bacteria. This article provides a novel strategy for the development of ultrasound-active metal-based antibiotics.
