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金纳米粒子修饰的中空碳体系用于肿瘤的双重响应释放和化疗-光热协同治疗。

Gold nanoparticles modified hollow carbon system for dual-responsive release and chemo-photothermal synergistic therapy of tumor.

机构信息

Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016, PR China.

Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016, PR China.

出版信息

J Colloid Interface Sci. 2019 Oct 15;554:239-249. doi: 10.1016/j.jcis.2019.07.005. Epub 2019 Jul 3.

Abstract

Thermochemotherapy has shown a synergistic anti-cancer efficiency and can enhance the therapeutic effect of simple chemotherapy. The photothermal conversion characteristics of carriers are vital in thermo-chemotherapy. Therefore, hollow mesoporous carbon (HMC) with excellent heating efficiency and a large specific surface area was used to ensure the high loading capacity. Next, approximately 4 nm spherical gold nanoparticles (NPs) were employed as gatekeepers of the tunnels of HMC by Au-S bonds, which have the same size as HMC mesopores. Additionally, the gold NPs could avoid the premature release of the drug and enhance the photothermal properties of the delivery system. The surface of the carriers was modified with polyethylene glycol (PEG) to increase the biocompatibility and dispersity of doxorubicin (DOX) loaded DOX/HMC-Au@PEG. DOX release was markedly accelerated in the presence of glutathione (GSH) and near-infrared (NIR), indicating that the system had redox and NIR dual-triggered drug release characteristics. Cytotoxicity experiments proved that combined therapy induced the highest cell killing level. Additionally, the combination index (CI) of DOX/HMC-Au@PEG was 0.452, indicating the synergistic effect of chemotherapy and photo-thermal therapy (PTT). In vivo antitumor experiments were also carried out and showed the same trend. In general, the results of this study indicated that DOX/HMC-Au@PEG has great potential in dual-triggered drug delivery and thermochemotherapy.

摘要

热化疗显示出协同的抗癌效率,并能增强单纯化疗的治疗效果。载体的光热转换特性在热化疗中至关重要。因此,使用具有高热效率和大比表面积的中空介孔碳(HMC)来确保高负载能力。接下来,通过 Au-S 键将大约 4nm 球形金纳米粒子(NPs)用作 HMC 隧道的守门员,其尺寸与 HMC 介孔相同。此外,金 NPs 可以避免药物的过早释放,并增强输送系统的光热性能。载体表面用聚乙二醇(PEG)进行修饰,以提高载阿霉素(DOX)的 DOX/HMC-Au@PEG 的生物相容性和分散性。在谷胱甘肽(GSH)和近红外(NIR)的存在下,DOX 的释放明显加快,表明该系统具有氧化还原和 NIR 双重触发的药物释放特性。细胞毒性实验证明联合治疗诱导了最高的细胞杀伤水平。此外,DOX/HMC-Au@PEG 的组合指数(CI)为 0.452,表明化学疗法和光热疗法(PTT)具有协同作用。体内抗肿瘤实验也显示出相同的趋势。总的来说,这项研究的结果表明,DOX/HMC-Au@PEG 在双重触发药物输送和热化疗方面具有很大的潜力。

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