School of Mechanical Systems Engineering, Chonnam National University, Gwangju, 500-757, Republic of Korea.
Nanotechnology. 2017 Oct 27;28(43):435102. doi: 10.1088/1361-6528/aa847f. Epub 2017 Aug 7.
In this study, a novel type of hyaluronic acid (HA)-decorated nanostructured lipid carrier (NLC) was prepared and investigated as a light-triggered drug release and combined photothermal-chemotherapy for cancer treatment. Polyhedral gold nanoparticles (Au NPs) with an average size of 10 nm were synthesized and co-encapsulated with doxorubicin (DOX) in the matrix of NLCs with a high drug loading efficiency (above 80%). HA decoration was achieved by the electrostatic interaction between HA and CTAB on the NLC surface. A remarkable temperature increase was observed by exposing the Au NP-loaded NLCs to an NIR laser, which heated the samples sufficiently (above 40 °C) to kill tumor cells. The entrapped DOX exhibited a sustained, stepwise NIR laser-triggered drug release pattern. The biocompatibility of the NLCs was investigated by MTT assay and the cell viability was maintained above 85%, even at high concentrations. The intracellular uptake of free DOX and entrapped DOX, observed by confocal microscopy, revealed two distinct uptake mechanisms, i.e. passive diffusion and endocytosis, respectively. In particular, internalization of the HA-Au-DOX-NLCs was more extensively enhanced than the Au-DOX-NLCs, which was attributed to HA-CD44 receptor-mediated endocytosis. Meanwhile, the internalized NLCs successfully escaped from the lysosomes, increasing the intracellular DOX. The HA-Au-DOX-NLCs IC value decreased from 2.3 to 0.6 μg ml with NIR irradiation at 72 h, indicating the excellent synergistic antitumor effect of photothermal-chemotherapy. The photothermal ablation was further confirmed by a live/dead cell staining assay. Thus, a combined photothermal-chemotherapy approach has been proposed as a promising strategy for cancer treatment.
在这项研究中，制备了一种新型的透明质酸（HA）修饰的纳米结构化脂质载体（NLC），并将其作为一种光触发药物释放和联合光热化疗的药物用于癌症治疗。合成了平均尺寸为 10nm 的多面金纳米粒子（Au NPs），并将其与阿霉素（DOX）共包封在具有高载药效率（超过 80%）的 NLC 基质中。HA 修饰是通过 HA 与 NLC 表面 CTAB 之间的静电相互作用实现的。将负载 Au NPs 的 NLC 暴露于近红外激光下，观察到显著的温度升高，足以使样品升温（超过 40°C）以杀死肿瘤细胞。包封的 DOX 表现出持续的、逐步的近红外激光触发药物释放模式。通过 MTT 测定法研究了 NLC 的生物相容性，即使在高浓度下，细胞活力仍保持在 85%以上。通过共聚焦显微镜观察到游离 DOX 和包封 DOX 的细胞内摄取，揭示了两种不同的摄取机制，即被动扩散和内吞作用。特别是，HA-Au-DOX-NLCs 的内化比 Au-DOX-NLCs 更广泛地增强，这归因于 HA-CD44 受体介导的内吞作用。同时，内化的 NLC 成功地从溶酶体中逃逸出来，增加了细胞内的 DOX。HA-Au-DOX-NLCs 的 IC 值在 72 小时近红外照射下从 2.3 降至 0.6μgml，表明光热化疗的协同抗肿瘤效果优异。通过活/死细胞染色试验进一步证实了光热消融。因此，提出了一种联合光热化疗的方法，作为癌症治疗的一种有前途的策略。
