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利用双功能聚乙烯亚胺笼状铂纳米簇对造血系统癌细胞进行选择性生物标记和诱导凋亡。

Selective bio-labeling and induced apoptosis of hematopoietic cancer cells using dual-functional polyethylenimine-caged platinum nanoclusters.

机构信息

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, NO. 1095, Jiefang Road, Wuhan, 430030, China.

School of Textiles, Zhongyuan University of Technology, No. 41, Zhongyuan Road (M), Zhengzhou, 450007, China.

出版信息

Biochem Biophys Res Commun. 2018 Sep 10;503(3):1465-1470. doi: 10.1016/j.bbrc.2018.07.064. Epub 2018 Jul 18.

Abstract

In the past decades, platinum (Pt) is employed to clinical treatment of various cancers. However, for Pt-based drugs, especially Pt in +2 state [Pt (II)], such as cisplatin, number of drawbacks impede their anticancer efficiency including poor pharmacology, fast blood clearance, systemic toxicities causing from poor specificity and excretion of drug through kidneys. Herein, we developed dual-functional ultrafine polyethylenimine caged platinum nanoclusters (PEI-caged Pt NCs), which were utilized in biological imaging of the suspension cells system as fluorescent markers, and selective inhibition of hematopoietic malignancies as anticancer chemotherapeutics simultaneously. These zerovalent Pt NCs are capable to selectively enter into blood cancer cells (K562, BV173 cell lines) when compared to the peripheral blood mononucleated cells (PBMCs) from healthy donors, in addition, it can specifically induce pro-apoptotic protein expression (p53, PUMA, cleaved caspase) in hematopoietic cancer cells and promote cell apoptosis. Avoiding the adding of other fluorescent bio-markers, these Pt NCs showed great potential in diagnosis and treatment of hematopoietic system disease, such as acute myeloid leukemia, lymphoma, myeloma, etc.

摘要

在过去几十年中,铂(Pt)被用于治疗各种癌症的临床治疗。然而,对于基于 Pt 的药物,特别是 +2 价态的 Pt(Pt(II)),如顺铂,许多缺点阻碍了它们的抗癌效率,包括较差的药理学、快速的血液清除、由于药物对肾脏的特异性差和排泄而引起的全身毒性。在此,我们开发了双功能超精细聚乙烯亚胺笼状铂纳米簇(PEI-cagedPtNCs),可同时用作悬浮细胞系统的荧光标记物进行生物成像,并选择性抑制血液系统恶性肿瘤作为抗癌化疗药物。与来自健康供体的外周血单核细胞(PBMCs)相比,这些零价 PtNCs 能够选择性地进入血液癌细胞(K562、BV173 细胞系),此外,它还可以在造血癌细胞中特异性诱导促凋亡蛋白表达(p53、PUMA、cleaved caspase)并促进细胞凋亡。避免添加其他荧光生物标志物,这些 PtNCs 在诊断和治疗造血系统疾病方面具有很大的潜力,如急性髓细胞白血病、淋巴瘤、骨髓瘤等。

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