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转铁蛋白偶联姜黄素载超顺磁性氧化铁纳米粒子诱导 K562 细胞增强摄取和凋亡。

Transferrin-conjugated curcumin-loaded superparamagnetic iron oxide nanoparticles induce augmented cellular uptake and apoptosis in K562 cells.

机构信息

Laboratory of Nanomedicine, Institute of Life Sciences, Nalco Square, Chandrasekharpur, Bhubaneswar 751023, Orissa, India.

出版信息

Acta Biomater. 2012 Feb;8(2):704-19. doi: 10.1016/j.actbio.2011.10.022. Epub 2011 Oct 22.

Abstract

Superparamagnetic iron oxide nanoparticles are currently used for precise drug delivery and as an image contrast agent. In the present study, the potentiality of curcumin-loaded magnetic nanoparticles (Cur-MNPs) for the treatment of chronic myeloid leukemia (CML) was investigated. For active therapy, transferrin (Tf) ligand was further conjugated to Cur-MNPs, which demonstrated enhanced uptake compared to Cur-MNPs in p210bcr/abl-positive cell line (K562). Cur-MNPs demonstrated greater and sustained anti-proliferative activity in a dose- and time-dependent manner; however, with the advent of a magnetic field the anti-proliferative activity of Cur-MNPs as well as Tf-Cur-MNPs was enhanced due to higher cellular uptake with enhanced cytotoxicity activity. Down-regulation of Bcr-Abl protein activates intrinsic apoptotic pathways for promoting anti-leukemic responses. Our in vitro results advocate potential clinical applications of Cur-MNPs by activating multiple signaling pathways for provoking the anti-leukemic activity.

摘要

超顺磁氧化铁纳米颗粒目前被用于精准药物递送和作为医学影像对比剂。在本研究中,负载姜黄素的磁性纳米颗粒(Cur-MNPs)在治疗慢性髓细胞白血病(CML)方面的潜力得到了研究。为了进行主动治疗,进一步将转铁蛋白(Tf)配体共轭到 Cur-MNPs 上,与 Cur-MNPs 相比,其在 p210bcr/abl 阳性细胞系(K562)中的摄取能力得到了增强。Cur-MNPs 以剂量和时间依赖的方式表现出更强和更持久的抗增殖活性;然而,随着磁场的出现,Cur-MNPs 以及 Tf-Cur-MNPs 的抗增殖活性由于更高的细胞摄取和增强的细胞毒性而得到增强。Bcr-Abl 蛋白的下调激活内在凋亡途径以促进抗白血病反应。我们的体外结果通过激活多种信号通路来引发抗白血病活性,为 Cur-MNPs 的潜在临床应用提供了依据。

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