To the Editor:Even to this day,the etiology and pathogenesis of inammatory bowel disease(IBD)are still unelucidated.Despite signicant progress in IBD treatment in recent years,some patients remain insensitive or non-r...To the Editor:Even to this day,the etiology and pathogenesis of inammatory bowel disease(IBD)are still unelucidated.Despite signicant progress in IBD treatment in recent years,some patients remain insensitive or non-responsive towards existing treatments.Therefore,further exploring IBD pathogenesis to develop novel therapeutic drugs or drug combinations is quite necessary.Recent studies have demonstrated the therapeutic potential of regulating cell death in IBD.The ferroptosis,a novel form of cell death,is also involved in the pathological process of IBD.展开更多
Glioma is a primary aggressive brain tumor with high recurrence rate.The poor efficiency of chemotherapeutic drugs crossing the blood-brain barrier(BBB) is well-known as one of the main challenges for anti-glioma ther...Glioma is a primary aggressive brain tumor with high recurrence rate.The poor efficiency of chemotherapeutic drugs crossing the blood-brain barrier(BBB) is well-known as one of the main challenges for anti-glioma therapy.Moreover,massive infiltrated tumor-associated macrophages(TAMs) in glioma further thwart the drug efficacy.Herein,a therapeutic nanosystem(SPP-ARV-825) is constructed by incorporating the BRD4-degrading proteolytic targeting chimera(PROTAC) ARV-825 into the complex micelle(SPP) composed of substance P(SP) peptide-modified poly(ethylene glycol)-poly(D,L-lactic acid)(SP-PEG-PDLL A) and methoxy poly(ethylene glycol)-poly(D,L-lac tic acid)(mPEG-PDLL A,PP),which could penetrate BBB and target brain tumor.Subsequently,released drug engenders antitumor effect via attenuating cells proliferation,inducing cells apoptosis and suppressing M2 macrophages polarization through the inhibition of IRF4 promoter transcription and phosphorylation of STAT6,STAT3 and AKT.Taken together,our work demonstrates the versatile role and therapeutic efficacy of SPP-ARV-825 micelle against glioma,which may provide a novel strategy for glioma therapy in future.展开更多
基金National Natural Science Foundation of China(Nos.82270565 and 82100565)Scientific research project of Tianjin Municipal Commission of Education(No.2022KJ243)
文摘To the Editor:Even to this day,the etiology and pathogenesis of inammatory bowel disease(IBD)are still unelucidated.Despite signicant progress in IBD treatment in recent years,some patients remain insensitive or non-responsive towards existing treatments.Therefore,further exploring IBD pathogenesis to develop novel therapeutic drugs or drug combinations is quite necessary.Recent studies have demonstrated the therapeutic potential of regulating cell death in IBD.The ferroptosis,a novel form of cell death,is also involved in the pathological process of IBD.
基金supported by the National Natural Science Foundation of China(No.82172630,81972347 and 82003493)the Key R&D Projects of the Science and Technology Department of Sichuan Province(No.2020YFS0213,China)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYJC21022,No.ZYYC21001 and 2019HXFH017,China)。
文摘Glioma is a primary aggressive brain tumor with high recurrence rate.The poor efficiency of chemotherapeutic drugs crossing the blood-brain barrier(BBB) is well-known as one of the main challenges for anti-glioma therapy.Moreover,massive infiltrated tumor-associated macrophages(TAMs) in glioma further thwart the drug efficacy.Herein,a therapeutic nanosystem(SPP-ARV-825) is constructed by incorporating the BRD4-degrading proteolytic targeting chimera(PROTAC) ARV-825 into the complex micelle(SPP) composed of substance P(SP) peptide-modified poly(ethylene glycol)-poly(D,L-lactic acid)(SP-PEG-PDLL A) and methoxy poly(ethylene glycol)-poly(D,L-lac tic acid)(mPEG-PDLL A,PP),which could penetrate BBB and target brain tumor.Subsequently,released drug engenders antitumor effect via attenuating cells proliferation,inducing cells apoptosis and suppressing M2 macrophages polarization through the inhibition of IRF4 promoter transcription and phosphorylation of STAT6,STAT3 and AKT.Taken together,our work demonstrates the versatile role and therapeutic efficacy of SPP-ARV-825 micelle against glioma,which may provide a novel strategy for glioma therapy in future.
