细胞内
IC50型
膀胱癌
癌症研究
体内
三磷酸腺苷
化学
生物物理学
癌症
药理学
医学
体外
生物
生物化学
内科学
生物技术
作者
Da‐Yong Hou,Ni-Yuan Zhang,Lu Wang,Ming Lv,Xiangpeng Li,Chengqi Zhang,Yue-Ze Wang,Lei Shen,Xiu-Hai Wu,Bo Fu,Peng Guo,Ziqi Wang,Dong‐Bing Cheng,Hao Wang,Wanhai Xu
摘要
Abstract Mitochondriopathy inspired adenosine triphosphate (ATP) depletions has been recognized as a powerful way for controlling tumor growth. Nevertheless, selective sequestration or exhaustion of ATP under complex biological environment remains a prodigious challenge. Harnessing the advantages of in vivo self-assembled nanomaterials, we designed an Intracellular ATP Sequestration (IAS) system to specifically construct nanofibrous nanostructures on the surface of tumor nuclear with exposed ATP binding site, leading to highly efficient suppression of bladder cancer by induction of mitochondriopathy-like damages. Briefly, the reported transformable nucleopeptide (NLS-FF-T) self-assembled into nuclear-targeted nanoparticles with ATP binding site encapsuled inside under aqueous conditions. By interaction with KPNA2, the NLS-FF-T transformed into nanofibrous-based ATP trapper on the surface of tumor nuclear, which prevented the intracellular energy production. As a result, multiple bladder tumor cell lines (T24, EJ and RT-112) revealed that the half-maximal inhibitory concentration (IC50) of NLS-FF-T was reduced by approximately 4-fold when compared to NLS-T. Following intravenously administration, NLS-FF-T was found to be dose-dependently accumulated at tumor site of T24 xenograft mice. More significantly, this IAS system exhibited an extremely antitumor efficacy according to the deterioration of T24 tumors and simultaneously prolonged the overall survival of T24 orthotopic xenograft mice. Together, our findings clearly demonstrated the therapeutic advantages of intracellular ATP sequestration induced mitochondriopathy-like damages, which provides a potential treatment strategy for malignancies.
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