College of Chemistry, Fuzhou University, 2 Xueyuan Road, Fuzhou 350116, China.
College of Biological Science and Engineering, Fuzhou University, 2 Xueyuan Road, Fuzhou 350116, China; Fujian Key Laboratory of Medical Instrument and Pharmaceutical Technology, Fuzhou University, 2 Xueyuan Road, Fuzhou 350116, China.
Int J Biol Macromol. 2023 Jul 1;242(Pt 3):125058. doi: 10.1016/j.ijbiomac.2023.125058. Epub 2023 May 25.
Rubropunctatin, a metabolite isolated from the fungi of the genus Monascus, is a natural lead compound applied for the suppression of tumors with good anti-cancer activity. However, its poor aqueous solubility has limited its further clinical development and utilization. Lecithin and chitosan are excellently biocompatible and biodegradable natural materials, which have been approved by the FDA as drug carrier. Here, we report for the first time the construction of a lecithin/chitosan nanoparticle drug carrier of the Monascus pigment rubropunctatin by electrostatic self-assembly between lecithin and chitosan. The nanoparticles are near-spherical with a size 110-120 nm. They are soluble in water and possess excellent homogenization capacity and dispersibility. Our in vitro drug release assay showed a sustained release of rubropunctatin. CCK-8 assays revealed that lecithin/chitosan nanoparticles loaded with rubropunctatin (RCP-NPs) had significantly enhanced cytotoxicity against mouse mammary cancer 4T1 cells. The flow cytometry results revealed that RCP-NPs significantly boosted cellular uptake and apoptosis. The tumor-bearing mice models we developed indicated that RCP-NPs effectively inhibited tumor growth. Our present findings suggest that lecithin/chitosan nanoparticle drug carriers improve the anti-tumor effect of the Monascus pigment rubropunctatin.
红曲色素 Rubropunctatin 是从红曲霉属真菌中分离得到的一种代谢产物，是一种天然的抗肿瘤先导化合物，具有良好的抗癌活性。然而，其较差的水溶性限制了其进一步的临床开发和利用。大豆卵磷脂和壳聚糖是极好的生物相容性和可生物降解的天然材料，已被 FDA 批准为药物载体。在这里，我们首次报道了通过大豆卵磷脂和壳聚糖之间的静电自组装构建红曲色素 Rubropunctatin 的大豆卵磷脂/壳聚糖纳米粒药物载体。纳米粒呈近球形，粒径为 110-120nm。它们可溶于水，具有良好的均化能力和分散性。我们的体外药物释放实验表明 Rubropunctatin 具有持续释放的特点。CCK-8 实验表明，负载 Rubropunctatin 的大豆卵磷脂/壳聚糖纳米粒（RCP-NPs）对小鼠乳腺癌 4T1 细胞具有显著增强的细胞毒性。流式细胞术结果表明 RCP-NPs 显著促进了细胞摄取和细胞凋亡。我们建立的荷瘤小鼠模型表明 RCP-NPs 能有效抑制肿瘤生长。我们的研究结果表明，大豆卵磷脂/壳聚糖纳米粒药物载体提高了红曲色素 Rubropunctatin 的抗肿瘤作用。
