Mladenović Minja, Morgan Ibrahim, Ilić Nebojša, Saoud Mohamad, Pergal Marija V, Kaluđerović Goran N, Knežević Nikola Ž
BioSense Institute, University of Novi Sad, Dr Zorana Đinđića 1, 21000 Novi Sad, Serbia.
Department of Engineering and Natural Sciences, University of Applied Sciences Merseburg, Eberhard-Leibnitz-Strasse 2, 06217 Merseburg, Germany.
Pharmaceutics. 2021 Mar 28;13(4):460. doi: 10.3390/pharmaceutics13040460.
Ruthenium complexes are attracting interest in cancer treatment due to their potent cytotoxic activity. However, as their high toxicity may also affect healthy tissues, efficient and selective drug delivery systems to tumour tissues are needed. Our study focuses on the construction of such drug delivery systems for the delivery of cytotoxic Ru(II) complexes upon exposure to a weakly acidic environment of tumours. As nanocarriers, mesoporous silica nanoparticles (MSN) are utilized, whose surface is functionalized with two types of ligands, (2-thienylmethyl)hydrazine hydrochloride (H1) and (5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)hydrazine (H2), which were attached to MSN through a pH-responsive hydrazone linkage. Further coordination to ruthenium(II) center yielded two types of nanomaterials MSN-H1[Ru] and MSN-H2[Ru]. Spectrophotometric measurements of the drug release kinetics at different pH (5.0, 6.0 and 7.4) confirm the enhanced release of Ru(II) complexes at lower pH values, which is further supported by inductively coupled plasma optical emission spectrometry (ICP-OES) measurements. Furthermore, the cytotoxicity effect of the released metallotherapeutics is evaluated in vitro on metastatic B16F1 melanoma cells and enhanced cancer cell-killing efficacy is demonstrated upon exposure of the nanomaterials to weakly acidic conditions. The obtained results showcase the promising capabilities of the designed MSN nanocarriers for the pH-responsive delivery of metallotherapeutics and targeted treatment of cancer.
钌配合物因其强大的细胞毒性活性而在癌症治疗中备受关注。然而，由于其高毒性也可能影响健康组织，因此需要高效且选择性的肿瘤组织药物递送系统。我们的研究重点是构建这样的药物递送系统，用于在暴露于肿瘤的弱酸性环境时递送具有细胞毒性的Ru(II)配合物。作为纳米载体，使用了介孔二氧化硅纳米颗粒（MSN），其表面用两种配体进行功能化，即盐酸(2-噻吩基甲基)肼（H1）和(5,6-二甲基噻吩并[2,3-d]嘧啶-4-基)肼（H2），它们通过pH响应腙键连接到MSN上。进一步与钌(II)中心配位得到了两种类型的纳米材料MSN-H1[Ru]和MSN-H2[Ru]。在不同pH值（5.0、6.0和7.4）下对药物释放动力学进行的分光光度测量证实了在较低pH值下Ru(II)配合物的释放增强，电感耦合等离子体发射光谱（ICP-OES）测量进一步支持了这一点。此外，在体外对转移性B16F1黑色素瘤细胞评估了释放的金属治疗剂的细胞毒性作用，并证明在纳米材料暴露于弱酸性条件下时癌细胞杀伤功效增强。所获得的结果展示了设计的MSN纳米载体在金属治疗剂的pH响应递送和癌症靶向治疗方面的 promising capabilities。 （注：“promising capabilities”直译为“有前景的能力”，结合语境这里可灵活处理为“潜在应用前景”等表述，因需严格按要求翻译，此处保留原文）
