Abstract:
Stimulus-responsive nanomaterials, particularly with targeting capabilities, have garnered significant attention in the cancer therapy. However, the biological safety of these innovative materials in vivo remains unknown, posing a hurdle to their clinical application. Here, a pH/H2O2 dual-responsive and targeting nano carrier system (NCS) was developed using core shell structure of Fe3O4 mesoporous silicon (MSN@Fe3O4) as main body, scutellarin (SCU) as antitumor drug and polymer cyclodextrin (PCD) as molecular switch (denoted as PCD@SCU@MSN@Fe3O4, abbreviated as NCS). The NCS, with an average particle size of 100 nm, displayed exceptional SCU loading capacity, a result of its uniform radial channel structure. The in vitro investigation under condition of pH and H2O2 indicated that NCS performed excellent pH/H2O2-triggered SCU release behavior. The NCS displayed a higher cytotoxicity against tumor cells (Huh7 and HCT116) due to its pH/H2O2 dual-triggered responsiveness, while the PCD@MSN@Fe3O4 demonstrated lower cytotoxicity for both Huh7 and HCT116 cells. In vivo therapeutic evaluation of NCS indicates significant inhibition of tumor growth in mouse subcutaneous tumor models, with no apparent side-effects detected. The NCS not only enhances the bioavailability of SCU, but also utilizes magnetic targeting technology to deliver SCU accurately to tumor sites. These findings underscore the substantial clinical application potential of NCS.
摘要:
刺激响应性纳米材料,特别是在瞄准能力方面,在癌症治疗中引起了极大的关注。然而,这些创新材料在体内的生物安全性仍然未知,对其临床应用构成障碍。这里,以Fe3O4介孔硅(MSN@Fe3O4)为主体,灯盏乙素(SCU)作为抗肿瘤药物,聚合物环糊精(PCD)作为分子开关(表示为PCD@SCU@MSN@Fe3O4,缩写为NCS)。NCS,平均粒径为100纳米,显示特殊的SCU负载能力,其均匀的径向通道结构的结果。在pH和H2O2条件下的体外研究表明,NCS具有优异的pH/H2O2触发的SCU释放行为。由于其pH/H2O2双重触发反应,NCS对肿瘤细胞(Huh7和HCT116)表现出更高的细胞毒性,而PCD@MSN@Fe3O4对Huh7和HCT116细胞均具有较低的细胞毒性。NCS的体内治疗性评估表明在小鼠皮下肿瘤模型中显著抑制肿瘤生长,没有检测到明显的副作用。NCS不仅提高了SCU的生物利用度,而且还利用磁靶向技术将SCU准确地输送到肿瘤部位。这些发现强调了NCS的巨大临床应用潜力。