Principe Gabriel, Lezcano Virginia, Tiburzi Silvina, Miravalles Alicia B, Rivero Paula S, Montiel Schneider María G, Lassalle Verónica, González-Pardo Verónica
Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS), San Juan 670, Bahía Blanca 8000, Argentina.
Instituto de Ciencias Biológicas y Biomédicas del Sur (INBIOSUR), UNS-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Bahía Blanca 8000, Argentina.
Pharmaceutics. 2023 Feb 1;15(2):488. doi: 10.3390/pharmaceutics15020488.
Magnetic nanosystems represent promising alternatives to the traditional diagnostic and treatment procedures available for different pathologies. In this work, a series of biological tests are proposed, aiming to validate a magnetic nanoplatform for Kaposi's sarcoma treatment. The selected nanosystems were polyethylene glycol-coated iron oxide nanoparticles (MAG.PEG), which were prepared by the hydrothermal method. Physicochemical characterization was performed to verify their suitable physicochemical properties to be administered in vivo. Exhaustive biological assays were conducted, aiming to validate this platform in a specific biomedical field related to viral oncogenesis diseases. As a first step, the MAG.PEG cytotoxicity was evaluated in a cellular model of Kaposi's sarcoma. By phase contrast microscopy, it was found that cell morphology remained unchanged regardless of the nanoparticles' concentration (1-150 µg mL). The results, arising from the crystal violet technique, revealed that the proliferation was also unaffected. In addition, cell viability analysis by MTS and neutral red assays revealed a significant increase in metabolic and lysosomal activity at high concentrations of MAG.PEG (100-150 µg mL). Moreover, an increase in ROS levels was observed at the highest concentration of MAG.PEG. Second, the iron quantification assays performed by Prussian blue staining showed that MAG.PEG cellular accumulation is dose dependent. Furthermore, the presence of vesicles containing MAG.PEG inside the cells was confirmed by TEM. Finally, the MAG.PEG steering was achieved using a static magnetic field generated by a moderate power magnet. In conclusion, MAG.PEG at a moderate concentration would be a suitable drug carrier for Kaposi's sarcoma treatment, avoiding adverse effects on normal tissues. The data included in this contribution appear as the first stage in proposing this platform as a suitable future theranostic to improve Kaposi's sarcoma therapy.
磁性纳米系统是针对不同病理状况的传统诊断和治疗程序的有前景的替代方案。在这项工作中，提出了一系列生物学测试，旨在验证用于治疗卡波西肉瘤的磁性纳米平台。所选的纳米系统是聚乙二醇包覆的氧化铁纳米颗粒（MAG.PEG），通过水热法制备。进行了物理化学表征，以验证其适合在体内给药的物理化学性质。进行了详尽的生物学测定，旨在在与病毒致癌疾病相关的特定生物医学领域中验证该平台。第一步，在卡波西肉瘤细胞模型中评估了MAG.PEG的细胞毒性。通过相差显微镜观察发现，无论纳米颗粒浓度（1 - 150 µg/mL）如何，细胞形态均保持不变。结晶紫技术的结果表明增殖也未受影响。此外，通过MTS和中性红测定进行的细胞活力分析显示，在高浓度的MAG.PEG（100 - 150 µg/mL）下，代谢和溶酶体活性显著增加。而且，在MAG.PEG的最高浓度下观察到活性氧水平升高。其次，普鲁士蓝染色进行的铁定量测定表明MAG.PEG在细胞内的积累呈剂量依赖性。此外，透射电子显微镜证实细胞内存在含有MAG.PEG的囊泡。最后，使用中等功率磁体产生的静磁场实现了MAG.PEG的操控。总之，中等浓度的MAG.PEG将是治疗卡波西肉瘤的合适药物载体，可避免对正常组织产生不良影响。本研究纳入的数据是将该平台作为未来改善卡波西肉瘤治疗的合适诊疗方法提出的第一阶段。
