Department of Biomedical Engineering, Technion-Israel Institute of Technology, Technion City, Haifa, 3200003, Israel.
Nanotechnology. 2018 May 4;29(18):185102. doi: 10.1088/1361-6528/aab00c. Epub 2018 Feb 16.
Copper oxide nanoparticles (CuO-NPs) are increasingly becoming the subject of investigation exploring their potential use for diagnostic and therapeutic purposes. Recent work has demonstrated their anticancer potential, as well as contrast agent capabilities for magnetic resonance imaging (MRI) and through-transmission ultrasound. However, no capability of CuO-NPs has been demonstrated using conventional ultrasound systems, which, unlike the former, are widely deployed in the clinic. Furthermore, in spite of their potential as multifunctional nano-based materials for diagnosis and therapy, CuO-NPs have been delayed from further clinical application due to their inherent toxicity. Herein, we present the synthesis of a novel nanoscale system, composed of CuO-loaded PLGA nanospheres (CuO-PLGA-NS), and demonstrate its imaging detectability and augmented heating effect by therapeutic ultrasound. The CuO-PLGA-NS were prepared by a double emulsion (W/O/W) method with subsequent solvent evaporation. They were characterized as sphere-shaped, with size approximately 200 nm. Preliminary results showed that the viability of PANC-1, human pancreatic adenocarcinoma cells was not affected after 72 h exposure to CuO-PLGA-NS, implying that PLGA masks the toxic effects of CuO-NPs. A systematic ultrasound imaging evaluation of CuO-PLGA-NS, using a conventional system, was performed in vitro and ex vivo using poultry heart and liver, and also in vivo using mice, all yielding a significant contrast enhancement. In contrast to CuO-PLGA-NS, neither bare CuO-NPs nor blank PLGA-NS possess these unique advantageous ultrasonic properties. Furthermore, CuO-PLGA-NS accelerated ultrasound-induced temperature elevation by more than 4 °C within 2 min. The heating efficiency (cumulative equivalent minutes at 43 °C) was increased approximately six-fold, demonstrating the potential for improved ultrasound ablation. In conclusion, CuO-PLGA-NS constitute a versatile platform, potentially useful for combined imaging and therapeutic ultrasound-based procedures.
氧化铜纳米颗粒（CuO-NPs）越来越成为研究的主题，探索其在诊断和治疗方面的潜在用途。最近的工作表明，它们具有抗癌潜力，以及磁共振成像（MRI）和透过式超声的对比剂能力。然而，CuO-NPs 尚未在常规超声系统中表现出任何能力，而常规超声系统与前者不同，在临床上广泛应用。此外，尽管它们作为多功能纳米基材料在诊断和治疗方面具有潜力，但由于其固有毒性，CuO-NPs 的进一步临床应用受到了阻碍。本文介绍了一种新型纳米级系统的合成，该系统由负载氧化铜的 PLGA 纳米球（CuO-PLGA-NS）组成，并通过治疗超声证明了其成像检测能力和增强的加热效果。CuO-PLGA-NS 采用双乳液（W/O/W）法制备，随后进行溶剂蒸发。它们被表征为球形，尺寸约为 200nm。初步结果表明，暴露于 CuO-PLGA-NS 72 小时后，人胰腺腺癌细胞 PANC-1 的活力没有受到影响，这意味着 PLGA 掩盖了 CuO-NPs 的毒性作用。使用常规系统对 CuO-PLGA-NS 进行了系统的超声成像评估，分别在体外和鸡心、鸡肝的离体以及小鼠体内进行了实验，均产生了显著的对比增强。与 CuO-PLGA-NS 相反，裸 CuO-NPs 和空白 PLGA-NS 均不具有这些独特的超声优势。此外，CuO-PLGA-NS 在 2 分钟内使超声诱导的温度升高超过 4°C。加热效率（43°C 时的累积等效分钟数）增加了约六倍，表明其具有提高超声消融的潜力。总之，CuO-PLGA-NS 构成了一个多功能平台，可能对联合成像和基于治疗超声的程序有用。
