College of Life Sciences, Zhejiang University, Hangzhou, China.
Institute of Hygiene, Zhejiang Academy of Medical Science, China.
Drug Deliv. 2020 Dec;27(1):491-501. doi: 10.1080/10717544.2020.1745327.
Injectable implants with the ability to form in situ are one of the most promising carriers for the delivery of chemotherapeutic drugs to tumor sites. We have reported a novel injectable in situ-forming implant system composed of n-butyl-2-cyanoacrylate (NBCA), ethyl oleate, along with the sol-gel phase transition. The chemotherapeutic drug-loaded injectable NBCA ethyl oleate implant (INEI) exhibited excellent therapeutic efficacy for local chemotherapy. Herein, we utilize this INEI to carry N, N'-(Sulfonyldi-4,1-phenylene)bis(2-chloroacetamide) (TE-C-5003), which is a selective protein arginine methyltransferase 1 (PRMT1) inhibitor, to treat the lung cancer mice model. The experiment shows that TE-C-5003 has a good anti-tumor effect on lung cancer (IC = 0.7022 µM for A549; IC = 0.6844 µM for NCL-H1299) and breast cancer (IC = 0.4128 µM for MCF-7; IC = 0.5965 µM for MDA-MB-231). Anti-tumor experiments in animal models showed that the average growth inhibition rate of xenografted human lung cancer cells by the TE-C-5003-loaded INEI (40% NBCA) was 68.23%, which is far more than TC-E-5003 alone (31.76%). Our study further confirms that INEI is an effective technique to improve the anti-tumor effect. The druggability of small molecule compounds can be improved with the help of the mentioned technology. Also, TC-E-5003 may be developed as a broad spectrum anti-tumor drug.
具有原位形成能力的可注射植入物是将化疗药物递送到肿瘤部位的最有前途的载体之一。我们已经报道了一种由 n-丁基-2-氰基丙烯酸酯（NBCA）、油酸乙酯以及溶胶-凝胶相转变组成的新型可注射原位形成植入系统。载药可注射 NBCA 油酸乙酯植入物（INEI）表现出优异的局部化疗疗效。在此，我们利用这种 INEI 携带 N，N'-(磺酰基二-4,1-亚苯基）双（2-氯乙酰胺）（TE-C-5003），这是一种选择性的蛋白质精氨酸甲基转移酶 1（PRMT1）抑制剂，用于治疗肺癌小鼠模型。实验表明，TE-C-5003 对肺癌（A549 的 IC = 0.7022 µM；NCL-H1299 的 IC = 0.6844 µM）和乳腺癌（MCF-7 的 IC = 0.4128 µM；MDA-MB-231 的 IC = 0.5965 µM）具有良好的抗肿瘤作用。动物模型中的抗肿瘤实验表明，负载 TE-C-5003 的 INEI（40% NBCA）对异种移植人肺癌细胞的平均生长抑制率为 68.23%，远高于单独使用 TE-C-5003（31.76%）。我们的研究进一步证实，INEI 是提高抗肿瘤效果的有效技术。在所述技术的帮助下，可以提高小分子化合物的成药性。此外，TE-C-5003 可能被开发为一种广谱抗肿瘤药物。
