Novel Oxygen-Deficient Zirconia (ZrO2–x) for Fluorescence/Photoacoustic Imaging-Guided Photothermal/Photodynamic Therapy for Cancer,ACS Applied Materials & Interfaces

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Novel Oxygen-Deficient Zirconia (ZrO2–x) for Fluorescence/Photoacoustic Imaging-Guided Photothermal/Photodynamic Therapy for Cancer
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2019-10-14 00:00:00 , DOI: 10.1021/acsami.9b16604
Lihong Sun _{1,

2} , Xiaodan Jiao _{1,

2} , Weiwei Liu ₃ , Ying Wang ₁ , Yang Cao ₃ , Shu-Juan Bao ₁ , Zhigang Xu _{1,

2} , Yuejun Kang _{1,

2} , Peng Xue _{1,

2}

Affiliation

Theranostic nanoplatforms that integrate therapy and diagnosis in a single composite have become increasingly attractive in the field of precise and efficient tumor treatment. Herein, a novel oxygen-deficient zirconia (ZrO_2–x) nanosystem based on the conjugation of thiol-polyethylene glycol-amine (SH-PEG-NH₂) and chlorin e6 (Ce6) was elaborately designed and established for efficacious photothermal/photodynamic therapy (PTT/PDT) and fluorescence/photoacoustic (FL/PA) bimodal imaging for the first time. The crystalline-disordered, PEGylated ZrO_2–x nanoparticles (ZP NPs) displayed strong optical absorption in the near-infrared (NIR) window and were featured with significant photothermal conversion capacity. The ZP NPs were further covalently conjugated with Ce6 to form ZrO_2–x@PEG/Ce6 (ZPC) NPs, which displayed a long circulatory half-life, efficient tumor accumulation, and outstanding FL/PA imaging performance. Moreover, the nanocomposites effectively generated cytotoxic intracellular reactive oxygen species (ROS) responsive to laser activation. Both cell studies and animal experiments explicitly demonstrated that ZPC NPs mediated remarkable tumor ablation with minimal systemic toxicity thanks to their tumor-specific PTT/PDT effect. Collectively, these findings may open up new avenues to broaden the application of oxygen-deficient ZrO_2–x nanostructures as high-performance photothermal agents in tumor theranostics through rational design and accurate control of their physiochemical properties.

中文翻译：

新型缺氧氧化锆（ZrO2-x）用于荧光/光声成像引导的光热/光动力疗法治疗癌症

将治疗和诊断整合在单个复合物中的治疗性纳米平台在精确和有效的肿瘤治疗领域中变得越来越有吸引力。在此，精心设计并建立了基于硫醇-聚乙二醇-胺（SH-PEG-NH ₂）和二氢卟酚e6（Ce6）结合的新型缺氧氧化锆（ZrO _{2– x}）纳米系统。疗法（PTT / PDT）和荧光/光声（FL / PA）双峰成像。结晶无序，聚乙二醇化的ZrO _2–_x纳米颗粒（ZP NPs）在近红外（NIR）窗口中显示出强大的光学吸收，并且具有显着的光热转换能力。ZP NPs与Ce6进一步共价结合形成ZrO _{2 – x} @ PEG / Ce6（ZPC）NPs，显示出长的循环半衰期，有效的肿瘤蓄积和出色的FL / PA成像性能。此外，纳米复合材料有效地产生了响应于激光激活的细胞毒性细胞内活性氧（ROS）。细胞研究和动物实验均清楚地表明，由于ZPC NP具有肿瘤特异性PTT / PDT的作用，因此它们介导了显着的肿瘤消融，具有最小的全身毒性。总的来说，这些发现可能为拓宽缺氧ZrO的应用开辟新途径。_{2- X}纳米结构通过合理的设计和它们的生理化学性质的准确控制在肿瘤治疗诊断学高性能光热剂。

更新日期：2019-10-15

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