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叶酸受体靶向的诊疗一体化 IrS 纳米粒子用于多模态成像引导的联合化疗-光热治疗。

Folate receptor-targeted theranostic IrS nanoparticles for multimodal imaging-guided combined chemo-photothermal therapy.

机构信息

MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, P. R. China.

出版信息

Nanoscale. 2018 Dec 21;10(47):22252-22262. doi: 10.1039/c8nr08095j. Epub 2018 Nov 22.

DOI:10.1039/c8nr08095j
PMID:30465053
Abstract

Nano-drug delivery systems with multi-modality imaging capacities are worth pursuing because they integrate diagnostic and therapeutic functions. Herein, we report the design, synthesis and evaluation of modified iridium sulfide (IrS) nanoparticles (NPs) for cancer therapy in vitro and in vivo. This nanosystem was prepared by modifying IrS with polyethylene glycol (PEG) conjugated to the targeting ligand folate (FA) for multimodal imaging-guided combined chemo-photothermal therapy. Upon PEG modification, the small IrS NPs (about 4 nm) self-assembled into much larger (about 120 nm) IrS-PEG-FA NPs, which exhibited high photostability, ideal photothermal effect, high drug loading and pH-/photothermal-responsive drug release properties. By using the model anticancer drug camptothecin (CPT), we demonstrated that CPT@IrS-PEG-FA can effectively target FA-receptor-positive cancer cells in vitro and show efficient tumor accumulation in vivo. The combination of CPT@IrS-PEG-FA treatment and irradiation with an 808 nm laser resulted in complete tumor elimination. Moreover, photothermal/photoacoustic (PA)/computed tomography (CT) imaging provided an effective means to monitor the therapeutic effects. Interestingly, the nanoparticles can be cleared, resulting in low systematic toxicity of CPT@IrS-PEG-FA. Our work demonstrates that the as-prepared IrS-PEG-FA NPs present a promising platform for the construction of multifunctional theranostic agents for cancer therapy.

摘要

具有多模式成像能力的纳米药物递送系统值得研究,因为它们集成了诊断和治疗功能。在此,我们报告了一种经修饰的硫化铱(IrS)纳米粒子(NPs)的设计、合成和评估,用于体外和体内癌症治疗。该纳米系统是通过用聚乙二醇(PEG)修饰 IrS 制备的,PEG 与靶向配体叶酸(FA)相连,用于多模式成像引导的联合化学-光热治疗。PEG 修饰后,小的 IrS NPs(约 4nm)自组装成更大的 IrS-PEG-FA NPs(约 120nm),具有高光稳定性、理想的光热效应、高载药率以及 pH/光热响应性药物释放特性。通过使用模型抗癌药物喜树碱(CPT),我们证明了 CPT@IrS-PEG-FA 可以有效地靶向 FA 受体阳性癌细胞,并在体内显示出有效的肿瘤积累。CPT@IrS-PEG-FA 联合 808nm 激光照射治疗可完全消除肿瘤。此外,光热/光声(PA)/计算机断层扫描(CT)成像为监测治疗效果提供了有效手段。有趣的是,纳米粒子可以被清除,导致 CPT@IrS-PEG-FA 的系统毒性低。我们的工作表明,所制备的 IrS-PEG-FA NPs 为构建用于癌症治疗的多功能治疗药物提供了一个有前途的平台。

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