Affiliated Hospital of Integrated Traditional Chinese and Western Medicine , Nanjing University of Chinese Medicine , Nanjing 210028 , China.
Jiangsu Provincial Academy of Traditional Chinese Medicine , Nanjing 210028 , China.
Mol Pharm. 2019 Dec 2;16(12):4826-4835. doi: 10.1021/acs.molpharmaceut.9b00717. Epub 2019 Oct 30.
Tumor-targeted ligand modification and nanosized coloaded drug delivery systems are promising for cancer therapy. In this study, we showed that coix seed oil and tripterine coloaded microemulsions with a transferrin modification (Tf-CT-MEs) could improve the treatment of cervical cancer. Tf-CT-MEs exhibited good stability in serum and a notably synergistic antiproliferation effect. In the HeLa xenograft tumor-bearing mouse model, Tf-CT-MEs accumulated at tumor sites and penetrated deeply in tumor tissues. Tf-CT-MEs had superior anticancer efficacy in vivo, which greatly slowed the growth of tumors (*** < 0.001 vs saline). We also found that Tf-CT-MEs inhibited tumor cell proliferation, enhanced antiangiogenesis, and induced apoptosis by regulating bax/bcl-2 and the activating caspase-3 pathway. Tf-CT-MEs decreased by 27.7, 26.9, 61.2, and 42.5% of concentrations of TGF-β1, CCL2, TNF-α, and IL-6 in serum, respectively. In addition, Tf-CT-MEs showed little toxicity in vital organs. These results were due to the improved drug delivery efficiency. Collectively, Tf-CT-MEs enhance tumor-targeting, facilitate deep penetration of drugs, and have promising potential as an efficient treatment for cervical cancer.
肿瘤靶向配体修饰和纳米级共载药物递送系统在癌症治疗中具有广阔的应用前景。本研究表明，转铁蛋白修饰的薏苡仁油和雷公藤红素共载微乳（Tf-CT-MEs）可提高宫颈癌的治疗效果。Tf-CT-MEs 在血清中具有良好的稳定性，并表现出显著的协同增殖抑制作用。在 HeLa 异种移植荷瘤小鼠模型中，Tf-CT-MEs 能够在肿瘤部位聚集并深入肿瘤组织。Tf-CT-MEs 在体内具有优越的抗癌疗效，大大减缓了肿瘤的生长（***<0.001 与生理盐水相比）。我们还发现，Tf-CT-MEs 通过调节 bax/bcl-2 和激活 caspase-3 通路抑制肿瘤细胞增殖、增强抗血管生成和诱导细胞凋亡。Tf-CT-MEs 使血清中 TGF-β1、CCL2、TNF-α 和 IL-6 的浓度分别降低了 27.7%、26.9%、61.2%和 42.5%。此外，Tf-CT-MEs 在重要器官中显示出较小的毒性。这些结果归因于提高了药物递送效率。综上所述，Tf-CT-MEs 增强了肿瘤靶向性，促进了药物的深层渗透，具有作为宫颈癌有效治疗方法的巨大潜力。
