Caro Carlos, Gámez Francisco, Quaresma Pedro, Páez-Muñoz Jose María, Domínguez Alejandro, Pearson John R, Pernía Leal Manuel, Beltrán Ana M, Fernandez-Afonso Yilian, De la Fuente Jesús M, Franco Ricardo, Pereira Eulália, García-Martín Maria Luisa
BIONAND-Centro Andaluz de Nanomedicina y Biotecnología (Junta de Andalucía-Universidad de Málaga), C/Severo Ochoa, 35, 29590 Málaga, Spain.
Departamento de Química Física, Universidad de Granada, Avenida de la Fuente Nueva S/N, 18071 Granada, Spain.
Pharmaceutics. 2021 Mar 20;13(3):416. doi: 10.3390/pharmaceutics13030416.
In this study, we report the synthesis of gold-coated iron oxide nanoparticles capped with polyvinylpyrrolidone (Fe@Au NPs). The as-synthesized nanoparticles (NPs) exhibited good stability in aqueous media and excellent features as contrast agents (CA) for both magnetic resonance imaging (MRI) and X-ray computed tomography (CT). Additionally, due to the presence of the local surface plasmon resonances of gold, the NPs showed exploitable "light-to-heat" conversion ability in the near-infrared (NIR) region, a key attribute for effective photothermal therapies (PTT). In vitro experiments revealed biocompatibility as well as excellent efficiency in killing glioblastoma cells via PTT. The in vivo nontoxicity of the NPs was demonstrated using zebrafish embryos as an intermediate step between cells and rodent models. To warrant that an effective therapeutic dose was achieved inside the tumor, both intratumoral and intravenous routes were screened in rodent models by MRI and CT. The pharmacokinetics and biodistribution confirmed the multimodal imaging CA capabilities of the Fe@AuNPs and revealed constraints of the intravenous route for tumor targeting, dictating intratumoral administration for therapeutic applications. Finally, Fe@Au NPs were successfully used for an in vivo proof of concept of imaging-guided focused PTT against glioblastoma multiforme in a mouse model.
在本研究中，我们报道了用聚乙烯吡咯烷酮包覆的金包覆氧化铁纳米颗粒（Fe@Au NPs）的合成。所合成的纳米颗粒（NPs）在水性介质中表现出良好的稳定性，并且作为磁共振成像（MRI）和X射线计算机断层扫描（CT）的造影剂（CA）具有优异的特性。此外，由于金的局域表面等离子体共振的存在，这些NPs在近红外（NIR）区域显示出可利用的“光热”转换能力，这是有效光热疗法（PTT）的关键属性。体外实验揭示了其生物相容性以及通过PTT杀死胶质母细胞瘤细胞的优异效率。使用斑马鱼胚胎作为细胞和啮齿动物模型之间的中间步骤，证明了NPs在体内的无毒性。为了确保在肿瘤内部达到有效的治疗剂量，通过MRI和CT在啮齿动物模型中筛选了瘤内和静脉内给药途径。药代动力学和生物分布证实了Fe@Au NPs的多模态成像CA能力，并揭示了静脉内途径在肿瘤靶向方面的局限性，这决定了治疗应用需采用瘤内给药。最后，Fe@Au NPs成功用于在小鼠模型中对多形性胶质母细胞瘤进行成像引导聚焦PTT的体内概念验证。
