Department of Pharmacy, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
Department of Chemistry, College of Basic Medicine, Army Medical University (Third Military Medical University), Chongqing, China.
Drug Deliv. 2021 Dec;28(1):1695-1708. doi: 10.1080/10717544.2021.1963351.
Luteolin (Lut) is a natural flavonoid polyphenolic compound with multiple pharmacological activities, such as anti-oxidant, anti-inflammatory, and anti-tumor effects. However, the poor aqueous solubility and low bioactivity of Lut restrict its clinical translation. Herein, we developed a reactive oxygen species (ROS)-responsive nanoplatforms to improve the bioactivity of Lut. Folic acid (FA) was employed to decorate the nanoparticles (NPs) to enhance its targeting ability. The size of Lut-loaded ROS-responsive nanoparticles (Lut/Oxi-αCD NPs) and FA-modified Lut/Oxi-αCD NPs (Lut/FA-Oxi-αCD NPs) is 210.5 ± 6.1 and 196.7 ± 1.8 nm, respectively. Both Lut/Oxi-αCD NPs and Lut/FA-Oxi-αCD NPs have high drug loading (14.83 ± 3.50 and 16.37 ± 1.47%, respectively). cellular assays verified that these NPs could be efficiently internalized by 4T1 cells and the released Lut from NPs could inhibit tumor cells proliferation significantly. Animal experiments demonstrated that Lut/Oxi-αCD NPs, especially Lut/FA-Oxi-αCD NPs obviously accumulated at tumor sites, and inhibited tumor growth ∼3 times compared to the Lut group. In conclusion, the antitumor efficacy of Lut was dramatically improved by targeting delivery with the ROS-responsive nanoplatforms.
木犀草素（Lut）是一种具有多种药理活性的天然类黄酮多酚化合物，具有抗氧化、抗炎和抗肿瘤作用。然而，Lut 的水溶解度差和生物活性低限制了其临床转化。在此，我们开发了一种活性氧（ROS）响应型纳米平台来提高 Lut 的生物活性。叶酸（FA）被用来修饰纳米颗粒（NPs）以增强其靶向能力。载有 Lut 的 ROS 响应型纳米颗粒（Lut/Oxi-αCD NPs）和 FA 修饰的 Lut/Oxi-αCD NPs（Lut/FA-Oxi-αCD NPs）的粒径分别为 210.5 ± 6.1 和 196.7 ± 1.8 nm。Lut/Oxi-αCD NPs 和 Lut/FA-Oxi-αCD NPs 的载药量均较高（分别为 14.83 ± 3.50%和 16.37 ± 1.47%）。细胞实验证实，这些 NPs 可以被 4T1 细胞有效内化，从 NPs 中释放的 Lut 可以显著抑制肿瘤细胞增殖。动物实验表明，与 Lut 组相比，Lut/Oxi-αCD NPs，特别是 Lut/FA-Oxi-αCD NPs 明显在肿瘤部位积聚，并抑制肿瘤生长约 3 倍。总之，通过 ROS 响应型纳米平台的靶向递送，显著提高了 Lut 的抗肿瘤疗效。
