纳米医学
三阴性乳腺癌
基因沉默
癌症研究
巴基斯坦卢比
糖酵解
材料科学
乳腺癌
小干扰RNA
小RNA
癌症
医学
化学
丙酮酸激酶
纳米技术
生物化学
转染
内科学
酶
纳米颗粒
基因
作者
Siming Huang,Wangshu Zhu,Fang Zhang,Guosheng Chen,Xiaoxue Kou,Xieqing Yang,Gangfeng Ouyang,Jun Shen
标识
DOI:10.1021/acsami.1c18053
摘要
Triple-negative breast cancer (TNBC) is typically associated with poor prognosis due to its only partial response to chemotherapy and lack of clinically established targeted therapies coupled with an aggressive disease course. Aerobic glycolysis is a hallmark of reprogrammed metabolic activity in cancer cells, which can be repressed by small-interfering RNA (siRNA). However, the lack of effective carriers to deliver vulnerable siRNA restricts the clinical potentials of glycolysis-based gene therapy for TNBC. Herein, we develop a tumor-targeted, biomimetic manganese dioxide (MnO2)-shrouded metal-organic framework (MOF) based nanomedicine to deliver siRNA against pyruvate kinase muscle isozyme M2 (siPKM2), wherein PKM2 is a rate-limiting enzyme in glycolysis, to inhibit the reprogrammed glycolysis of TNBC. This MOF-based genetic nanomedicine shows excellent monodispersity and stability and protects siPKM2 against degradation by nucleases. The nanomedicine not only substantially blocks the glycolytic pathway but also improves intracellular hypoxia in TNBC cells, with a resultant O2-enhanced anticancer effect. In the mice orthotopic TNBC model, the nanomedicine shows a remarkable therapeutic effect. Meanwhile, the Mn2+ ions released from acid microenvironment-responsive MnO2 enable in vivo monitoring of the therapeutic process with magnetic resonance imaging (MRI). Our study shows great promise with this MRI-visible MOF-based nanomedicine for treating TNBC by inhibition of glycolysis via the RNA interference.
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