叶黄素纳米载药用于治疗黑色素瘤。
Luteolin-Loaded Nanoparticles for the Treatment of Melanoma.
机构信息
Shanghai Skin Disease Clinical College, The Fifth Clinical Medical College, Anhui Medical University, Shanghai Skin Disease Hospital, Shanghai, 200443, People's Republic of China.
Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200011, People's Republic of China.
出版信息
Int J Nanomedicine. 2023 Apr 20;18:2053-2068. doi: 10.2147/IJN.S400329. eCollection 2023.
BACKGROUND AND PURPOSE
Luteolin (LUT), a flavonoid found in various plants, has been reported to have potential therapeutic effects in melanoma. However, poor water solubility and low bioactivity have severely restricted the clinical application of LUT. Based on the high reactive oxygen species (ROS) levels in melanoma cells, we developed nanoparticles encapsulating LUT with the ROS-responsive material poly(propylene sulfide)-poly(ethylene glycol) (PPS-PEG) to enhance the water solubility of LUT, accelerate the release of LUT in melanoma cells, and further enhance its anti-melanoma effect, providing a viable solution for the application of LUT nano-delivery systems in melanoma therapy.
METHODS
In this study, LUT-loaded nanoparticles were prepared with PPS-PEG and named as LUT-PPS-NPs. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) were applied to determine the size and morphology of LUT-PPS-NPs. In vitro studies were carried out to determine the uptake and mechanism of LUT-PPS-NPs by SK-MEL-28 melanoma cells. According to the CCK-8 assay, the cytotoxic effects of LUT-PPS-NPs on human skin fibroblasts (HSF) and SK-MEL-28 cells were assessed. Apoptosis assays, cell migration and invasion assays, and proliferation inhibition assays with low and normal density plating were also applied to test the in vitro anti-melanoma effect. Additionally, melanoma models were established utilizing BALB/c nude mice and initially evaluated the growth inhibitory impact following intratumoral injection of LUT-PPS-NPs.
RESULTS
The size of LUT-PPS-NPs was 169.77 ± 7.33 nm with high drug loading (15.05 ± 0.07%). In vitro, cellular assays confirmed that LUT-PPS-NPs were efficiently internalized by SK-MEL-28 cells and showed low cytotoxicity against HSF. Moreover, LUT released from LUT-PPS-NPs significantly inhibited tumor cell proliferation, migration and invasion. Animal experiments showed that LUT-PPS-NPs inhibited tumor growth more than 2-fold compared with the LUT group.
CONCLUSION
In conclusion, the LUT-PPS-NPs developed in our study enhanced the anti-melanoma effect of LUT.
背景与目的
木犀草素（LUT）是一种存在于多种植物中的类黄酮，已被报道具有治疗黑色素瘤的潜在疗效。然而，较差的水溶性和低生物活性严重限制了 LUT 的临床应用。基于黑色素瘤细胞中高活性氧（ROS）水平，我们开发了一种用 ROS 响应性材料聚（丙烯基硫醚）-聚（乙二醇）（PPS-PEG）包封 LUT 的纳米粒子，以提高 LUT 的水溶性，加速 LUT 在黑色素瘤细胞中的释放，并进一步增强其抗黑色素瘤作用，为 LUT 纳米递药系统在黑色素瘤治疗中的应用提供了可行的解决方案。
方法
在这项研究中，我们使用 PPS-PEG 制备了负载 LUT 的纳米粒子，并将其命名为 LUT-PPS-NPs。动态光散射（DLS）和透射电子显微镜（TEM）用于确定 LUT-PPS-NPs 的大小和形态。通过体外研究，确定 LUT-PPS-NPs 被 SK-MEL-28 黑色素瘤细胞摄取的机制和途径。根据 CCK-8 测定法，评估 LUT-PPS-NPs 对人皮肤成纤维细胞（HSF）和 SK-MEL-28 细胞的细胞毒性作用。还应用凋亡检测、细胞迁移和侵袭检测以及低和正常密度接种的增殖抑制检测来测试体外抗黑色素瘤作用。此外，利用 BALB/c 裸鼠建立黑色素瘤模型，并初步评价了 LUT-PPS-NPs 瘤内注射后的生长抑制作用。
结果
LUT-PPS-NPs 的粒径为 169.77±7.33nm，载药率高（15.05±0.07%）。体外细胞实验证实，LUT-PPS-NPs 能被 SK-MEL-28 细胞有效内化，并对 HSF 表现出低细胞毒性。此外，LUT-PPS-NPs 释放的 LUT 显著抑制肿瘤细胞增殖、迁移和侵袭。动物实验表明，与 LUT 组相比，LUT-PPS-NPs 能使肿瘤生长抑制超过 2 倍。
结论
总之，本研究中开发的 LUT-PPS-NPs 增强了 LUT 的抗黑色素瘤作用。
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