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Development and Characterization of Ultrasound Activated Lipopolyplexes for Enhanced Transfection by Low Frequency Ultrasound in In Vitro Tumor Model.
Macromolecular Bioscience ( IF 4.6 ) Pub Date : 2020-09-03 , DOI: 10.1002/mabi.202000173
Hirva Shah 1 , Imran Tariq 1, 2 , Konrad Engelhardt 1 , Udo Bakowsky 1 , Shashank Reddy Pinnapireddy 1, 3
Affiliation  

This work focuses on the development of ultrasound contrast vesicles for ultrasound‐mediated enhanced transfection of nucleic acids in the cancer cells and projects its application as a tool for diagnostic imaging. The ultrasound contrast vesicles are stable, anionic, nanoscaled vesicles with ultrasound contrast equivalent to the commercially available SonoVue. These anionic lipid vesicles establish electrostatic interaction with cationic polyplexes based on linear polyethylenimine (22kDa) forming lipopolyplexes with ultrasound contrast. The lipopolyplexes are characterized regarding shape, size, and zeta potential. When exposed to low frequency ultrasound, these carriers show elevated transfection efficiency and reduced cytotoxicity. The effect of post‐transfection ultrasound on cellular uptake of lipopolyplexes is also evaluated. An analogous transfection is also observed in the tumor mimicking multicellular 3D spheroid culture of ovarian cancer cells. The emergence of tumor imaging and enhanced gene delivery by medical ultrasound, a noninvasive imaging modality, is considered paving the way for efficient theranostic gene therapy.

中文翻译:

用于体外肿瘤模型中低频超声增强转染的超声活化脂多聚复合物的开发和表征。

这项工作的重点是超声造影囊泡的开发,用于超声介导的癌细胞中核酸的增强转染,并将其作为诊断成像工具的应用。超声造影囊泡是稳定的阴离子纳米级囊泡,其超声对比度与市售的 SonoVue 相当。这些阴离子脂质囊泡与基于线性聚乙烯亚胺 (22kDa) 的阳离子复合物建立静电相互作用,形成具有超声对比的脂质复合物。脂质复合物的特征在于形状、大小和 zeta 电位。当暴露于低频超声时,这些载体表现出转染效率提高和细胞毒性降低。还评估了转染后超声对脂质复合物细胞摄取的影响。在模拟卵巢癌细胞的多细胞 3D 球体培养物的肿瘤中也观察到类似的转染。肿瘤成像和医学超声增强基因传递的出现,一种非侵入性成像方式,被认为为有效的治疗诊断基因治疗铺平了道路。
更新日期:2020-09-03
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