结直肠癌正在全球范围内成为最常见的癌症之一，患病率和死亡率均排名前三。口服甲氨蝶呤（MTX）已被用作各种癌症的一线治疗药物，如结直肠癌、乳腺癌和肺癌。然而，胃肠道微环境的复杂性和特异性以及MTX本身的局限性，包括严重的不良反应和不稳定性，是安全输送MTX到结直肠肿瘤部位的主要障碍。本文介绍了一种创新的口服抗癌治疗药物MTX@Am7CD/SDS NPs，具有pH和温度敏感性，可以有效防止MTX@Am7CD/SDS NPs在模拟胃和小肠的酸性环境中被降解，从而有潜力在结直肠病变部位积累，并在温和条件下进一步释放肠道药物。细胞实验中，与游离的MTX相比，MTX@Am7CD/SDS NPs在三个肿瘤细胞系上显示出良好的抑制肿瘤效果，并对SW480细胞显示出优异的细胞摄取能力和诱导细胞凋亡的效果。因此，该研究为安全使用MTX治疗结直肠癌甚至其他肠道疾病提供了可行的解决方案。© 2023 Wiley-VCH GmbH.

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.© 2023 Wiley-VCH GmbH.