School of Pharmacy, Anhui University of Chinese Medicine, Anhui Academy of Chinese Medicine, Hefei, Anhui 230012, China.
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, P. R. China.
Mol Pharm. 2021 Mar 1;18(3):1470-1479. doi: 10.1021/acs.molpharmaceut.1c00030. Epub 2021 Feb 14.
To enhance the water solubility, oral bioavailability, and tumor targeting of gambogenic acid (GNA), polydopamine nanoparticles (PDA NPs) were prepared to encapsulate and stabilize GNA surface modified by folic acid (FA) and then coated with sodium alginate (GNA@PDA-FA SA NPs) to achieve an antitumor effect by oral administration. GNA@PDA-FA SA NPs exhibited pH-sensitive release behavior. cell studies manifested that GNA@PDA-FA NPs had higher cytotoxicity to 4T1 cells compared with raw GNA (IC = 2.58 μM 7.57 μM). After being modified with FA, GNA@PDA-FA NPs were taken up easily by 4T1 cells. studies demonstrated that the area under the curve (AUC) of the plasma drug concentration-time of GNA@PDA-FA SA NPs was 2.97-fold higher than that of raw GNA, along with improving drug distribution in the liver, lung, and kidney tissues. anti-tumor experiments, GNA@PDA-FA SA NPs significantly inhibited the growth of breast tumors in the 4T1 xenograft breast cancer model oral administration without obvious toxicity on major organs. Our studies indicated that the GNA@PDA-FA SA NPs modified with FA and coated with SA were a promising drug delivery system for targeting tumor therapy oral administration.
为了提高 Gambogenic 酸（GNA）的水溶性、口服生物利用度和肿瘤靶向性，制备了聚多巴胺纳米粒子（PDA NPs），以包裹和稳定经叶酸（FA）表面修饰的 GNA，然后用海藻酸钠（GNA@PDA-FA SA NPs）进行涂层，通过口服给药实现抗肿瘤作用。GNA@PDA-FA SA NPs 表现出 pH 敏感的释放行为。细胞研究表明，与原 GNA 相比，GNA@PDA-FA NPs 对 4T1 细胞具有更高的细胞毒性（IC = 2.58 μM vs. 7.57 μM）。经 FA 修饰后，GNA@PDA-FA NPs 容易被 4T1 细胞摄取。研究表明，GNA@PDA-FA SA NPs 的血浆药物浓度-时间曲线下面积（AUC）是原 GNA 的 2.97 倍，同时改善了药物在肝、肺和肾组织中的分布。在抗肿瘤实验中，GNA@PDA-FA SA NPs 显著抑制了 4T1 异种移植乳腺癌模型中乳腺癌的生长，口服给药对主要器官没有明显毒性。我们的研究表明，经 FA 修饰和 SA 涂层的 GNA@PDA-FA SA NPs 是一种有前途的靶向肿瘤治疗的口服给药药物递送系统。
