Connective tissue growth factor(CTGF) is a key driver in the pathogenesis of idiopathic pulmonary fibrosis(IPF). This study presents a groundbreaking supramolecular cryoshock bone marrow mononuclear cell system for ta...Connective tissue growth factor(CTGF) is a key driver in the pathogenesis of idiopathic pulmonary fibrosis(IPF). This study presents a groundbreaking supramolecular cryoshock bone marrow mononuclear cell system for targeted drug delivery in IPF. We incorporated antisense oligonucleotides(ASO) to inhibit CTGF and simultaneously encapsulated nintedanib using the ZMO-E5-NPs carrier for synergistic delivery. The cryoshock treatment enhances cellular structural integrity and preserves receptor functionality,thereby extending cell viability. By modifying the E5 peptide and conjugating it with DSPEPEG-MAL, we developed a composite carrier, ZMO-E5-NPs, which demonstrates efficient lung-targeting capability. This system enables rapid nanoparticle capture by fibroblasts through matrix metalloproteinase 2(MMP2) recognition, ensuring precise delivery of both ASO and nintedanib. In a bleomycin-induced pulmonary fibrosis mouse model, ZMOE5-NPs-ASO(nintedanib-containing group) significantly attenuated fibrosis progression,improved lung function, and exhibited excellent biocompatibility and safety, highlighting its potential as a novel therapeutic strategy for respiratory diseases.展开更多
A one-pot synthesis of vicinal diamines using indoles,azoles and phenothiazines in a tandem multi-component reaction is developed.The utilization of a copper-iodine co-catalytic system enables the generation of a dive...A one-pot synthesis of vicinal diamines using indoles,azoles and phenothiazines in a tandem multi-component reaction is developed.The utilization of a copper-iodine co-catalytic system enables the generation of a diverse range of vicinal diaminoindoles with good selectivity and moderate to good yields.An attractive aspect of this method is that it can be conducted under mild and environmentally friendly conditions,showcasing its potential as an alternative approach for synthesizing vicinal diamines.Moreover,the use of a multicomponent tandem reaction highlights the power and versatility of such strategies in synthetic chemistry.展开更多
基金supported by The National Natural Science Foundation of China (Grant Numbers 82400094, 82270069, 82370073)National High Level Hospital Clinical Research Funding (2022-PUMCH-B-108)。
文摘Connective tissue growth factor(CTGF) is a key driver in the pathogenesis of idiopathic pulmonary fibrosis(IPF). This study presents a groundbreaking supramolecular cryoshock bone marrow mononuclear cell system for targeted drug delivery in IPF. We incorporated antisense oligonucleotides(ASO) to inhibit CTGF and simultaneously encapsulated nintedanib using the ZMO-E5-NPs carrier for synergistic delivery. The cryoshock treatment enhances cellular structural integrity and preserves receptor functionality,thereby extending cell viability. By modifying the E5 peptide and conjugating it with DSPEPEG-MAL, we developed a composite carrier, ZMO-E5-NPs, which demonstrates efficient lung-targeting capability. This system enables rapid nanoparticle capture by fibroblasts through matrix metalloproteinase 2(MMP2) recognition, ensuring precise delivery of both ASO and nintedanib. In a bleomycin-induced pulmonary fibrosis mouse model, ZMOE5-NPs-ASO(nintedanib-containing group) significantly attenuated fibrosis progression,improved lung function, and exhibited excellent biocompatibility and safety, highlighting its potential as a novel therapeutic strategy for respiratory diseases.
基金the National Natural Science Foundation of China(22201048)the Natural Science Foundation of Guangxi Province(2022GXNSFBA035480)+1 种基金the Specific Research Project of Guangxi for Research Bases and Talents(2022AC21099)the Start-up Fund of Guangxi University(A3040051013)for financial support.
文摘A one-pot synthesis of vicinal diamines using indoles,azoles and phenothiazines in a tandem multi-component reaction is developed.The utilization of a copper-iodine co-catalytic system enables the generation of a diverse range of vicinal diaminoindoles with good selectivity and moderate to good yields.An attractive aspect of this method is that it can be conducted under mild and environmentally friendly conditions,showcasing its potential as an alternative approach for synthesizing vicinal diamines.Moreover,the use of a multicomponent tandem reaction highlights the power and versatility of such strategies in synthetic chemistry.
