College of Chemistry and Chemical Engineering, Yunnan Normal University, Kunming, 650500, P. R. China.
Shenzhen Kewode Technology Co., Ltd, Shenzhen, 518028, P. R. China.
Chempluschem. 2023 Nov;88(11):e202300387. doi: 10.1002/cplu.202300387. Epub 2023 Oct 6.
Colon cancer is emerging as one of the most common cancers worldwide, ranking in the top three in morbidity and mortality. Oral methotrexate (MTX) has been employed as a first-line treatment for various cancers, such as colon, breast, and lung cancer. However, the complexity and particularity of the gastrointestinal microenvironment and the limitations of MTX itself, including severe adverse effects and instability, are the main obstacles to the safe delivery of MTX to colon tumor sites. Herein, an innovative oral administrated anticancer therapeutic MTX@Am7CD/SDS NPs equipped with both pH and temperature sensitivity, which could effectively prevent MTX@Am7CD/SDS NPs from being degraded in the acidic environment mimicking the stomach and small intestine, thus harboring the potential to accumulate at the site of colon lesions and further release intestinal drug under mild conditions. In cellular assays, compared with free MTX, MTX@Am7CD/SDS NPs showed a favorable tumor inhibition effect on three tumor cell lines, as well as excellent cell uptake and apoptosis-inducing effect on SW480 cells. Therefore, this work provides a feasible solution for the safe use of MTX in the treatment of colon cancer and even other intestinal diseases.
结肠癌正在成为全球最常见的癌症之一，在发病率和死亡率方面排名前三。口服甲氨蝶呤（MTX）已被用作多种癌症的一线治疗药物，如结肠癌、乳腺癌和肺癌。然而，胃肠道微环境的复杂性和特殊性以及 MTX 本身的局限性，包括严重的不良反应和不稳定性，是 MTX 安全递送到结肠癌肿瘤部位的主要障碍。在此，我们开发了一种创新的口服抗癌治疗药物 MTX@Am7CD/SDS NPs，它具有 pH 和温度双重敏感性，能够有效防止 MTX@Am7CD/SDS NPs 在模拟胃和小肠的酸性环境中被降解，从而有可能在结肠病变部位积累，并在温和条件下进一步释放肠道药物。在细胞实验中，与游离 MTX 相比，MTX@Am7CD/SDS NPs 对三种肿瘤细胞系表现出良好的肿瘤抑制作用，并且对 SW480 细胞具有优异的细胞摄取和诱导细胞凋亡作用。因此，这项工作为 MTX 在结肠癌甚至其他肠道疾病的治疗中的安全应用提供了一种可行的解决方案。
