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Internalization by PMMA nanoparticle-mediated endocytosis of a survivin molecular beacon as theranostic agent in human cancer cells

机译:PMMA纳米粒子介导的内化介导的Survivin分子信标作为人癌细胞中的治疗剂的内吞作用

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One of the main goals in nanomedicine is the development of effective drug delivery systems. Polymeric nanoparticles(NPs) have been exploited as nanocarriers for their stability, handiness and biocompatibility. In this context, NPs havebeen coupled to molecular beacons (MBs), theranostic agents that conjugate the sensing of specific mRNA with asilencing activity.The aim of this work was to evaluate by confocal microscopy and fluorescence measurements: a) the involvement ofendocytosis in the NP uptake; b) the NP fate at different times of cell incubation to verify their localization in lysosomes;c) the MB localization on the Endoplasmic Reticulum (ER) where the target mRNA is located.Results: a) PMMA-NPs promote endocytosis; b) strong co-localization of NP and lysosome tracker fluorescence after 2-48 hours of incubation; c) co-localization of the MB fluorescence with the ER-marker signal after 90' of incubation.The data highlight the ability of the PMMA-NPs to promote the survivin-MB internalization by endocytosis anddemonstrate that the PMMA-NPs are an appropriate delivery system capable of being eliminated by cells; theseevidences also contribute to consider the MB as an effective tool for the intracellular sensing.
机译:纳米医生的主要目标之一是有效药物递送系统的发展。聚合物纳米颗粒(NPS)已被利用为纳米载波,以稳定,方便,生物相容性。在这方面,NPS有结合到分子信标(MBS),治疗剂与缀合特定mRNA的感测沉默活动。这项工作的目的是通过共聚焦显微镜和荧光测量来评估:a)参与NP吸收中的内吞作用; b)在不同时间的细胞孵育时NP命运,以验证它们在溶酶体中的定位;c)在靶mRNA所在的内质网(ER)上的MB定位。结果:A)PMMA-NPS促进内吞作用; b)2-后的NP和溶酶体跟踪器荧光的强烈共定位孵化48小时; c)MB荧光与90'孵育后的ER标记信号的共定位。该数据突出了PMMA-NPS通过内吞作用促进Survivin-MB内化的能力和证明PMMA-NPS是能够被细胞消除的适当递送系统;这些证据还有助于将MB视为细胞内传感的有效工具。

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