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Label-Free Raman Microspectral Analysis for Comparison of Cellular Uptake and Distribution between Non-Targeted and EGFR-Targeted Biodegradable Polymeric Nanoparticles

机译:无标记拉曼显微光谱分析用于比较非靶向和EGFR靶向的可生物降解聚合物纳米颗粒的细胞吸收和分布

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摘要

Active targeted delivery of nanoparticle-encapsulated agents to tumor cells in vivo is expected to enhance therapeutic effect with significantly less non-specific toxicity. Active targeting is based on surface modification of nanoparticles with ligands that bind with extracellular targets and enhance payload delivery in the cells. In this study, we have used label-free Raman micro-spectral analysis and kinetic modeling to study cellular interactions and intracellular delivery of C6-ceramide using a non-targeted and an epidermal growth factor receptor (EGFR) targeted biodegradable polymeric nano-delivery systems, in EGFR-expressing human ovarian adenocarcinoma (SKOV3) cells. The results show that EGFR peptide-modified nanoparticles were rapidly internalized in SKOV3 cells leading to significant intracellular accumulation as compared to non-specific uptake by the non-targeted nanoparticles. Raman micro-spectral analysis enables visualization and quantification of the carrier system, drug-load, and responses of the biological systems interrogated, without exogenous staining and labeling procedures.
机译:预期将纳米颗粒包封的药剂主动靶向递送至体内肿瘤细胞可提高治疗效果,且非特异性毒性明显降低。主动靶向是基于纳米颗粒的表面修饰,该纳米颗粒具有与细胞外靶标结合并增强细胞中有效负载传递的配体。在这项研究中,我们使用了无标记的拉曼光谱分析和动力学模型来研究使用非靶向和表皮生长因子受体(EGFR)靶向的可生物降解聚合物纳米递送系统对C6-神经酰胺的细胞相互作用和细胞内递送,在表达EGFR的人卵巢腺癌细胞(SKOV3)中。结果表明,与非靶向纳米颗粒的非特异性摄取相比,EGFR肽修饰的纳米颗粒在SKOV3细胞中快速内在化,从而导致明显的细胞内积累。拉曼显微光谱分析无需外部染色和标记程序,就可以可视化和定量分析载体系统,载药量以及所询问的生物系统的反应。

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