Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.
Department of Biomedical Science and BK21 PLUS Centre for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
J Control Release. 2018 Jun 28;280:20-30. doi: 10.1016/j.jconrel.2018.04.050. Epub 2018 May 1.
In this study, we developed novel hyaluronic acid cross-linked zein nanogels (HA-Zein NGs) to deliver the potential anticancer agent curcumin (CRC), a naturally occurring phytochemical drug in cancer cells. In vitro studies showed that they are highly compatible with the tested cell lines. They showed CD44 specific uptake in CT26 cell line more than by the CD44 receptor pre-inhibited CT26 cells. The CRC encapsulated HA-Zein NGs (HA-Zein-CRC NGs) found to exert a specific toxicity against CT26 sparing healthy normal fibroblast cells in vitro. The apoptotic effects were further confirmed with flow cytometry showing that the HA-Zein-CRC NGs exhibited high anticancer activity against the CT26 cells. The in vivo bio-distribution with a CT26 tumor model showed their high tumor accumulation thereby improved antitumor efficacy with a low dosage of CRC, compared to the previous reports. Thus, the preclinical studies clearly showed that these novel HA-Zein NGs would be highly beneficial in encapsulating hydrophobic drugs with improved pharmacokinetics thereby enhancing the therapeutic outcomes.
在这项研究中,我们开发了新型的透明质酸交联玉米醇溶蛋白纳米凝胶(HA-Zein NGs),以输送潜在的抗癌药物姜黄素(CRC),这是一种存在于癌细胞中的天然植物化学药物。体外研究表明,它们与测试的细胞系高度兼容。它们在 CT26 细胞系中表现出 CD44 特异性摄取,而在 CD44 受体预先抑制的 CT26 细胞中摄取较少。载有 CRC 的 HA-Zein NGs(HA-Zein-CRC NGs)被发现对 CT26 具有特异性毒性,而对体外健康的正常成纤维细胞没有毒性。流式细胞术进一步证实了凋亡作用,表明 HA-Zein-CRC NGs 对 CT26 细胞具有很高的抗癌活性。在 CT26 肿瘤模型中的体内生物分布显示,与之前的报告相比,它们具有很高的肿瘤积累,从而以低剂量 CRC 提高了抗肿瘤疗效。因此,临床前研究清楚地表明,这些新型的 HA-Zein NGs 将非常有利于包封疏水性药物,从而改善药代动力学,提高治疗效果。