多药耐药（MDR）在结直肠癌术后化疗期间的发展大大降低了治疗效果。可修改化学性质的纳米结构药物传递系统（NDDSs）被视为可逆转结直肠癌细胞中MDR的有希望的候选治疗方法。掺杂硒的磷酸锰（Se-MnP）纳米颗粒（NPs）通过持续释放硒可以逆转药物耐受性，有改善结直肠癌化疗效果的潜力。Se-MnP NPs具有有机无机杂化的组成，由较小尺度的纳米团聚体组装而成。Se-MnP NPs通过Se介导的STAT3/JNK途径和银离子（Mn2+）存在引起的类Fenton反应诱导过度的ROS生成。此外，体内外研究表明，Se-MnP NPs是奥沙利铂（OX）的有效药物载体，可逆转多药耐药并在结直肠癌细胞中诱导caspase介导的凋亡。OX@Se-MnP NPs通过下调MDR相关的ABC（ATP结合盒）转运蛋白（例如ABCB1，ABCC1和ABCG2）的表达来逆转结直肠癌中的MDR 。最后，体内研究表明，载有OX的Se-MnP NPs显著抑制了裸鼠中OX耐药HCT116（HCT116/DR）肿瘤细胞的增殖。具有简单制备和生物仿生化学性质的OX@Se-MnP NPs代表了治疗MDR结直肠癌的有希望的候选药物。 ©2023. 作者（们）。

The development of multidrug resistance (MDR) during postoperative chemotherapy for colorectal cancer substantially reduces therapeutic efficacy. Nanostructured drug delivery systems (NDDSs) with modifiable chemical properties are considered promising candidates as therapies for reversing MDR in colorectal cancer cells. Selenium-doped manganese phosphate (Se-MnP) nanoparticles (NPs) that can reverse drug resistance through sustained release of selenium have the potential to improve the chemotherapy effect of colorectal cancer.Se-MnP NPs had an organic-inorganic hybrid composition and were assembled from smaller-scale nanoclusters. Se-MnP NPs induced excessive ROS production via Se-mediated activation of the STAT3/JNK pathway and a Fenton-like reaction due to the presence of manganese ions (Mn2+). Moreover, in vitro and in vivo studies demonstrated Se-MnP NPs were effective drug carriers of oxaliplatin (OX) and reversed multidrug resistance and induced caspase-mediated apoptosis in colorectal cancer cells. OX@Se-MnP NPs reversed MDR in colorectal cancer by down-regulating the expression of MDR-related ABC (ATP binding cassette) transporters proteins (e.g., ABCB1, ABCC1 and ABCG2). Finally, in vivo studies demonstrated that OX-loaded Se-MnP NPs significantly inhibited proliferation of OX-resistant HCT116 (HCT116/DR) tumor cells in nude mice.OX@Se-MnP NPs with simple preparation and biomimetic chemical properties represent promising candidates for the treatment of colorectal cancer with MDR.© 2023. The Author(s).