Ilinskaya Olga, Yakovleva Galina, Zelenikhin Pavel, Kolpakov Alexey, Kurdy William, Glukhov Mikhail, Sedov Igor, Kharintsev Sergey
Microbiology Department, Institute of Fundamental Medicine and Biology of Kazan (Volga-Region) Federal University, Kazan Federal University, Kremlevskaya St., 18, Kazan 420008, Russia.
Mineralogy and Lithology Department, Institute of Geology and Oil and Gas Technologies of Kazan (Volga-Region) Federal University, Kazan Federal University, Kremlevskaya St., 4/5, Kazan 420111, Russia.
Int J Mol Sci. 2025 Sep 20;26(18):9205. doi: 10.3390/ijms26189205.
Blocking the MAPK pathway is a strategy to stop cancer cells proliferation. Despite all the successes, the acquisition of drug resistance by cells, as well as the mutational status of the downstream protein KRAS, reduces the tumor response to therapy. Ribonuclease binase from is among the agents that block this pathway through direct interaction with EGFR and RAS. The present study is aimed at the design, optimization, and characterization of a novel complex based on antitumor binase immobilized on microgranular clinoptilolite-containing rock to ensure its prolonged release in the gastrointestinal tract. A set of modern methods including transmission electron microscopy, scanning electron microscopy, and computed tomography was used to characterize the granularity, porosity and elemental composition of the carrier. The size of binase particles, measured by atomic force microscopy at 7 nm, allows enzyme penetration into meso- and macropores of the carrier. Calorimetric results confirm that binase is stable at high temperatures, even exceeding those in the body, and retains catalytic activity in the model fluids of the gastrointestinal tract. The parameters for processing a natural clinoptilolite-containing rock and the conditions for binase sorption were selected. The gradual release of the enzyme from the carrier lasts over 20 h, which provides cytotoxicity towards human adenocarcinoma cells during movement through the gastrointestinal tract. Thus, for the first time a promising long-acting complex with antitumor and detoxifying properties was successfully created.
阻断丝裂原活化蛋白激酶（MAPK）信号通路是一种阻止癌细胞增殖的策略。尽管取得了诸多成功，但细胞获得耐药性以及下游蛋白KRAS的突变状态会降低肿瘤对治疗的反应。来自[具体来源未提及]的核糖核酸酶binase是通过与表皮生长因子受体（EGFR）和RAS直接相互作用来阻断该信号通路的药物之一。本研究旨在设计、优化并表征一种新型复合物，该复合物基于固定在含斜发沸石的微颗粒岩石上的抗肿瘤binase，以确保其在胃肠道中能持续释放。使用了包括透射电子显微镜、扫描电子显微镜和计算机断层扫描在内的一系列现代方法来表征载体的粒度、孔隙率和元素组成。通过原子力显微镜测量，binase颗粒大小为7纳米，这使得酶能够渗透到载体的中孔和大孔中。量热结果证实，binase在高温下甚至超过人体温度时仍保持稳定，并在胃肠道模拟液中保留催化活性。选择了处理天然含斜发沸石岩石的参数以及binase的吸附条件。酶从载体中的逐渐释放持续超过20小时，这在其通过胃肠道的过程中对人腺癌细胞产生细胞毒性。因此，首次成功制备了一种具有抗肿瘤和解毒特性的有前景的长效复合物。
