Cruz Nuno, Pinho Jacinta Oliveira, Soveral Graça, Ascensão Lia, Matela Nuno, Reis Catarina, Gaspar Maria Manuela
Instituto de Biofísica e Engenharia Biomédica (IBEB), Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal.
Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
Nanomaterials (Basel). 2020 Apr 6;10(4):693. doi: 10.3390/nano10040693.
Cancer is a major health concern and the prognosis is often poor. Significant advances in nanotechnology are now driving a revolution in cancer detection and treatment. The goal of this study was to develop a novel hybrid nanosystem for melanoma treatment, integrating therapeutic and magnetic targeting modalities. Hence, we designed long circulating and pH-sensitive liposomes loading both dichloro(1,10-phenanthroline) copper (II) (Cuphen), a cytotoxic metallodrug, and iron oxide nanoparticles (IONPs). The synthetized IONPs were characterized by transmission electron microscopy and dynamic light scattering. Lipid-based nanoformulations were prepared by the dehydration rehydration method, followed by an extrusion step for reducing and homogenizing the mean size. Liposomes were characterized in terms of incorporation parameters and mean size. High Cuphen loadings were obtained and the presence of IONPs slightly reduced Cuphen incorporation parameters. Cuphen antiproliferative properties were preserved after association to liposomes and IONPs (at 2 mg/mL) did not interfere on cellular proliferation of murine and human melanoma cell lines. Moreover, the developed nanoformulations displayed magnetic properties. The absence of hemolytic activity for formulations under study demonstrated their safety for parenteral administration. In conclusion, a lipid-based nanosystem loading the cytotoxic metallodrug, Cuphen, and displaying magnetic properties was successfully designed.
癌症是一个主要的健康问题，其预后往往很差。纳米技术的重大进展正在推动癌症检测和治疗的一场革命。本研究的目的是开发一种用于黑色素瘤治疗的新型混合纳米系统，整合治疗和磁靶向模式。因此，我们设计了一种长效循环且对pH敏感的脂质体，其负载了二氯（1,10-菲咯啉）铜（II）（Cuphen），一种细胞毒性金属药物，以及氧化铁纳米颗粒（IONPs）。合成的IONPs通过透射电子显微镜和动态光散射进行表征。基于脂质的纳米制剂通过脱水再水化方法制备，随后进行挤压步骤以减小并均一化平均尺寸。脂质体根据包封参数和平均尺寸进行表征。获得了高的Cuphen负载量，并且IONPs的存在略微降低了Cuphen的包封参数。Cuphen与脂质体结合后其抗增殖特性得以保留，并且IONPs（浓度为2 mg/mL）对小鼠和人黑色素瘤细胞系的细胞增殖没有干扰。此外，所开发的纳米制剂表现出磁性。所研究的制剂没有溶血活性，证明了它们用于肠胃外给药的安全性。总之，成功设计了一种负载细胞毒性金属药物Cuphen并具有磁性的基于脂质的纳米系统。
