Department of Cell Biology, Physiology and Immunology, Faculty of Sciences, University of Cordoba, 14014 Cordoba, Spain.
Department of Physical Chemistry, Faculty of Chemistry, University of Seville, 41012 Seville, Spain.
Int J Mol Sci. 2022 Dec 8;23(24):15575. doi: 10.3390/ijms232415575.
Different gold nanosystems covered with DNA and doxorubicin (Doxo) were designed and synthesized for cancer therapy, starting from Au@16-Ph-16 cationic nanoparticles and DNA-Doxo complexes prepared under saturation conditions. For the preparation of stable, biocompatible, and small-sized compacted Au@16-Ph-16/DNA-Doxo nanotransporters, the conditions for the DNA-Doxo compaction process induced by gold nanoparticles were first explored using fluorescence spectroscopy, circular dichroism and atomic force microscopy techniques. The reverse process, which is fundamental for Doxo liberation at the site of action, was found to occur at higher C concentrations using these techniques. Zeta potential, dynamic light scattering and UV-visible spectroscopy reveal that the prepared compacted nanosystems are stable, highly charged and of adequate size for the effective delivery of Doxo to the cell. This fact is verified by in vitro biocompatibility and internalization studies using two prostate cancer-derived cell lines (LNCaP and DU145) and one hepatocellular carcinoma-derived cell line (SNU-387), as well as a non-tumor prostate (PNT2) cell line and a non-hepatocarcinoma hepatoblastoma cell line (Hep-G2) model used as a control in liver cells. However, the most outstanding results of this work are derived from the use of the C+N combined treatments which present strong action in cancer-derived cell lines, while a protective effect is observed in non-tumor cell lines. Hence, novel therapeutic targets based on gold nanoparticles denote high selectivity compared to conventional treatment based on free Doxo at the same concentration. The results obtained show the viability of both the proposed methodology for internalization of compacted nanocomplexes inside the cell and the effectiveness of the possible treatment and minimization of side effects in prostate and liver cancer.
设计并合成了不同的金纳米系统,这些系统覆盖有 DNA 和阿霉素 (Doxo),用于癌症治疗,其起始原料为在饱和条件下制备的 Au@16-Ph-16 阳离子纳米颗粒和 DNA-Doxo 复合物。为了制备稳定、生物相容且尺寸较小的紧凑型 Au@16-Ph-16/DNA-Doxo 纳米转运体,首先使用荧光光谱法、圆二色性和原子力显微镜技术探索了金纳米颗粒诱导 DNA-Doxo 压缩过程的条件。发现,使用这些技术,在更高的 C 浓度下会发生对于在作用部位释放 Doxo 至关重要的反过程。Zeta 电位、动态光散射和紫外可见光谱表明,所制备的紧凑型纳米系统稳定、带高电荷且尺寸适当,可有效将 Doxo 递送至细胞。这一事实通过使用两种前列腺癌细胞系 (LNCaP 和 DU145) 和一种肝癌细胞系 (SNU-387) 以及非肿瘤前列腺 (PNT2) 细胞系和非肝癌肝癌细胞系 (Hep-G2) 模型进行体外生物相容性和内化研究得到了验证,这些模型用作肝细胞中的对照。然而,这项工作的最突出结果源自 C+N 联合治疗的使用,这种治疗在癌症衍生的细胞系中具有强大的作用,而在非肿瘤细胞系中观察到保护作用。因此,与相同浓度的游离 Doxo 常规治疗相比,基于金纳米颗粒的新型治疗靶标具有高选择性。所获得的结果表明,所提出的方法在将紧凑型纳米复合物内化到细胞内的可行性以及在前列腺癌和肝癌中的潜在治疗效果和最小化副作用方面是有效的。