【摘 要】
：
Recently,PtⅣ prodrugs have attracted much attention as the next generation of platinum-based antineoplastic drug candidates.Here we report the discovery and evaluation of monochalcoplatin,a monocarbox
【机 构】
：
College of Chemistry & Environmental Science,Hebei University,Baoding,071002;Key Laboratory of Medic
论文部分内容阅读
Recently,PtⅣ prodrugs have attracted much attention as the next generation of platinum-based antineoplastic drug candidates.Here we report the discovery and evaluation of monochalcoplatin,a monocarboxylated PtⅣ prodrug that is among the most cvtoioxic PtⅣ prodrugs to date.Compared with its dicarboxylated counterparr chalcoplatin,monochalcoplatin accumulates astonishingly effectively and rapidly in cancer cells,which is not ascribed to its lipophilicity.The prodrug is quickly reduced,causes DNA damage,and induces apoptosis,resulting in superior cytotoxiciry with IC50 values in the nanomolar range in both cisplatin-sensitive and-resistant cells; these IC50 values are up t0 422-fold higher than that of cisplatin.A detailed mechanistic study reveals that monochalcoplatin acrively enters cells through a transporter-mediated process.Moreover,monochalcoplatin shows significant antitumor activity m an in vivo colorectal tumor model.Our study implies a practical strategy for the design of more effective PtⅣ prodrugs to conquer drug resistance by tuning both cellular uptake pathways and activation processes.
其他文献
肺组织代谢过程中需要丰富的血流，消耗大量的氧气和营养物质，代谢产生的废物以及疾病状态下的修复和代偿就需要更多的途径来转运和排出。近些年胶质淋巴系统的研究，使脑内淋巴系统这个概念得到了重新的关注。一些研究表明，颅内淋巴可能不存在固定的淋巴管引流途径，而是在脑组织的内部特别是血管周围间隙，可能存在功能性诱导性开放的组织问隙，充当淋巴管的功能，仍旧可以发挥清除脑内一些大分子的作用；经由此路径山颅，最终汇
随着能源需求的转型,作为重要的核工业原料和战略资源,铀元素受到越来越多的重视.由于全世界范围内铀矿储量的极不平均,导致绝大多数国家和地区缺乏铀矿.与陆地矿产相比,海水中虽然铀酰基离子的浓度仅为13.7 nM,但因为地球71％的面积为海洋,所以储量巨大.因此,从海洋资源中富集金属铀具有长远的战略意义.目前高效富集海水中的铀元素依然是世界性的难题,伴随生命科学的发展和人类对蛋白质结构功能认识的加深,经
Pyrophosphate(ppi),as an extremely significant biological anion,play a key role in hydrolysis and synthesis of ATP and DNA and several major metabolic processes[1].In bioinorganic systems,benzimidazol
光动力疗法(PDT)是一种利用活性氧杀死癌细胞的治疗方法.铱(Ⅲ)配合物呈三重激发态,可与周围氧分子(O2)之间发生能量转移,诱导产生单线态氧(1O2),因此可以作为光敏剂在光照射下直接或间接地杀死癌细胞.[1,2]内质网(ER)是细胞非常重要的的细胞器,主要负责蛋白质和膜脂质的合成和输出.内质网氧化还原信号通路的细微干扰都很可能导致内质网应激诱导的细胞凋亡.鉴于此,我们介绍了一系列以ER 为目标
Vanadium complexes are promismg anti-diabetic agents.The key issue of rational drug design of anti-diabetic vanadium complexes will still be how to balance the potential toxicity aud pharmacological a
钌络合物作为DNA分子“光开关”得到广泛研究[1],但由于其较低的膜通透性,其活细胞内的直接成像实例较少.我们的研究表明[Ru(5,5-dtbpy)2dppz]2+(Ru)(dtbpy = 4,4-二叔丁基-2,2-联吡啶；dppz =多吡啶并吩嗪)具有亲脂性强,对癌细胞与正常细胞具有选择性,且与氯代酚形成亲脂性离子对复合物后可快速进入细胞乃至细胞核,并引起细胞凋亡.我们基于此前研究[2],对bp
活细胞的pH 值测定对于更好地了解细胞功能和疾病早期诊断具有十分重要的意义。在这项工作中,我们采用一锅法合成了碳化氮-碱性品红(graphitic carbon nitride-fuchsin,以下简称CN-f)纳米探针,实现活细胞内pH 值的测定。
本文设计了基于Fe3+与羧苄西林形成的MOF 材料(carMOF)的纳米载药体系.首先将TPZ 负载到介孔二氧化硅(MSN)中,之后在MSN 的表面包覆一层carMOF.外层的carMOF可以有效保护内部的TPZ,避免了TPZ 的提前释放.最后再吸附GOx,形成最终的材料MSN-TPZ@carMOF-GOx.终材料可以消耗葡萄糖,从而加重肿瘤微环境的乏氧程度,增强了TPZ 的化疗活性,达到饥饿治疗
Vanadium compounds exhibit potent anti-diabetic [1],anti-cancer [2] and anti-Alzheimer disease activity [3].Previously,the molecular mechanisms of vanadium compounds on improving the glucose/lipid met
核磁共振造影剂可以增强成像病灶位置与背景的信号对比度来提高核磁磁共振成像(MRI)的准确性[1]。但是，磁共振成像(MRI)造影剂的低灵敏度是当前急需解决的问题。