Mao Xiaoman, Calero-Pérez Pilar, Montpeyó David, Bruna Jordi, Yuste Victor J, Candiota Ana Paula, Lorenzo Julia, Novio Fernando, Ruiz-Molina Daniel
Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST, Campus UAB, Cerdanyola del Vallès, 08193 Barcelona, Spain.
Centro de Investigación Biomédica en Red: Bioingeniería, Biomateriales y Nanomedicina, Cerdanyola del Vallès, 08193 Barcelona, Spain.
Nanomaterials (Basel). 2022 Apr 5;12(7):1221. doi: 10.3390/nano12071221.
Cisplatin has been described as a potent anticancer agent for decades. However, in the case of glioblastomas, it is only considered a rescue treatment applied after the failure of second-line treatments. Herein, based on the versatility offered by coordination chemistry, we engineered nanoparticles by reaction of a platinum (IV) prodrug and iron metal ions showing in vitro dual pH- and redox-sensitivity, controlled release and comparable cytotoxicity to cisplatin against HeLa and GL261 cells. In vivo intranasal administration in orthotopic preclinical GL261 glioblastoma tumor-bearing mice demonstrated increased accumulation of platinum in tumors, leading in some cases to complete cure and prolonged survival of the tested cohort. This was corroborated by a magnetic resonance imaging follow-up, thus opening new opportunities for intranasal glioblastoma therapies while minimizing side effects. The findings derived from this research showed the potentiality of this approach as a novel therapy for glioblastoma treatment.
几十年来,顺铂一直被视为一种有效的抗癌药物。然而,对于胶质母细胞瘤而言,它仅被视为二线治疗失败后应用的挽救性治疗方法。在此,基于配位化学提供的多功能性,我们通过铂(IV)前药与铁金属离子反应制备了纳米颗粒,该纳米颗粒在体外表现出双pH和氧化还原敏感性、可控释放,并且对HeLa细胞和GL261细胞具有与顺铂相当的细胞毒性。在原位临床前GL261胶质母细胞瘤荷瘤小鼠中进行的体内鼻内给药证明,铂在肿瘤中的蓄积增加,在某些情况下导致受试组完全治愈并延长生存期。磁共振成像随访证实了这一点,从而为鼻内胶质母细胞瘤治疗开辟了新机会,同时将副作用降至最低。这项研究得出的结果表明,这种方法作为胶质母细胞瘤治疗的新疗法具有潜力。