平方毫米
癌症研究
癌症治疗
存水弯(水管)
纳米技术
纳米颗粒
癌症
肽
材料科学
生物
细胞凋亡
医学
内科学
生物化学
工程类
环境工程
作者
Fangzhou Li,Delin Chen,Qianqian Sun,Jiale Wu,Yaling Gan,Kam W. Leong,Xing‐Jie Liang
标识
DOI:10.1002/adma.202305164
摘要
Gene mutations and functional inhibition are the major obstacles for p53-mediated oncotherapy. For p53-wild-type tumors, the underlying mechanisms of functional inhibition of p53 during oncogenesis are unknown. The results reveal that the expression of the MDM2 inhibitor ARF is inhibited in p53-wild-type tumors, indicating that the restoration of ARF could be a potential oncotherapy strategy for p53-wild-type tumors. Therefore, ARF-mimetic MDM2-targeting reassembly peptide nanoparticles (MtrapNPs) for p53-based tumor therapy is developed. The results elucidated that the MtrapNPs respond to and form a nanofiber structure with MDM2. By trapping MDM2, the MtrapNPs stabilize and activate p53 for the inhibition of p53-wild-type tumors. In most cases, reactivated mutant p53 is inhibited and degraded by MDM2. In the present study, MtrapNPs are used to load and deliver arsenic trioxide, a p53 mutation rescuer, for p53-mutated tumor treatment in both orthotopic and metastatic models, and they exhibit significant therapeutic effects. Therefore, the study provides evidence supporting a link between decreased ARF expression and tumor development in patients with p53-wild-type tumors. Thus, the MDM2-trap strategy, which addresses both the inhibition and mutations of p53, is an efficient strategy for the treatment of p53-mutated tumors.
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