Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL_(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL_(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.

Objective This study was mainly focused on styudy on he proteome profile change between exposure to 1-Bromopropane (1-BP) and 1-BP poisoning.Methods The samples of serums from exposure to 1-BP and 1-BP poisoning were collected and analyzed through Label free proteome technology platform.The differently expressed proteins between the two groups were quantified and identified,followed by function analysis by bioinformatics.Results 127 proteins over 2 fold-change were selected,in which 39 proteins were up-regulated and 88 proteins were down-regulated.These differently expressed proteins were mainly involved in the process of enzyme active regulation,inflammatory reaction,protein modification,stress response,coagulation,transport.Conclusion The differently expressed proteins provided the potential protein biomarkers for the early diagnosis of 1-BP poisoning and was beneficial for clinical diagnosis of 1-BP and understanding of the mechanism of 1-BP poisoning.

Objective This study was mainly focused on styudy on he proteome profile change between exposure to 1-Bromopropane (1-BP) and 1-BP poisoning.Methods The samples of serums from exposure to 1-BP and 1-BP poisoning were collected and analyzed through Label free proteome technology platform.The differently expressed proteins between the two groups were quantified and identified,followed by function analysis by bioinformatics.Results 127 proteins over 2 fold-change were selected,in which 39 proteins were up-regulated and 88 proteins were down-regulated.These differently expressed proteins were mainly involved in the process of enzyme active regulation,inflammatory reaction,protein modification,stress response,coagulation,transport.Conclusion The differently expressed proteins provided the potential protein biomarkers for the early diagnosis of 1-BP poisoning and was beneficial for clinical diagnosis of 1-BP and understanding of the mechanism of 1-BP poisoning.