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近红外二区光热治疗联合谷胱甘肽耗竭的多模态成像引导耐缺氧化学动力学-光催化-光热肿瘤协同治疗体系:基于单一激光触发。

Near-Infrared II Plasmonic Phototheranostics with Glutathione Depletion for Multimodal Imaging-Guided Hypoxia-Tolerant Chemodynamic-Photocatalytic-Photothermal Cancer Therapy Triggered by a Single Laser.

机构信息

School of Materials Science and Engineering, Central South University, Changsha, Hunan, 410083, China.

出版信息

Small. 2022 Jan;18(4):e2105638. doi: 10.1002/smll.202105638. Epub 2021 Nov 25.


DOI:10.1002/smll.202105638
PMID:34821041
Abstract

Tumor microenvironment (TME)-activatable phototheranostics is highly desirable in cancer management but still remains challenging for clinical applications owing to the lack of multifunctional theranostic agents and the limited tissue penetration depth. Reported here is an "all-in-one" phototheranostic platform based on near-infrared II (NIR-II) dual-plasmonic Au@Cu Se core-shell nanocrystals (dpGCS NCs) for combined photoacoustic (PA)/photothermal (PT) imaging-guided chemodynamic therapy (CDT)/photocatalytic therapy (PCT)/photothermal therapy (PTT) all triggered by a single NIR-II laser. The dpGCS NCs feature excellent NIR-II plasmonic and PT properties, which guarantee their capabilities of NIR-II PA and PT imaging for real-time visual observation of tumor size and location during cancer treatment. Additionally, the TME-activated in situ •OH production via dpGCS NC-catalyzed Fenton-like reaction is further enhanced by the NIR-II irradiation, while photoexcited plasmonic hole-induced formation of extra •OH is also evidenced for PCT. Both in vitro and in vivo experiments confirm remarkable therapeutic efficacy of the present phototheranostic platform under NIR-II laser through the CDT/PCT/PTT trimodal combination therapy, achieving complete inhibition of tumor growth in tumor-bearing mice after administration of dpGCS NCs plus a single NIR-II laser irradiation. This work provides a distinctive paradigm for the development of NIR-II phototheranostic platforms for imaging-guided cancer therapy using a single laser.

摘要

肿瘤微环境(TME)激活的光疗诊断在癌症管理中是非常需要的,但由于缺乏多功能治疗剂和有限的组织穿透深度,在临床应用中仍然具有挑战性。本文报道了一种基于近红外二区(NIR-II)双等离子体金@铜硒核壳纳米晶体(dpGCS NCs)的“一体化”光疗诊断平台,可用于联合光声(PA)/光热(PT)成像引导的化学动力学治疗(CDT)/光催化治疗(PCT)/光热治疗(PTT),所有这些都可以通过单个 NIR-II 激光触发。dpGCS NCs 具有优异的近红外二区等离子体和 PT 性能,保证了其在癌症治疗过程中实时观察肿瘤大小和位置的近红外二区 PA 和 PT 成像能力。此外,通过 dpGCS NC 催化的芬顿样反应,TME 激活的原位•OH 生成在 NIR-II 照射下进一步增强,而光激发等离子体空穴诱导的额外•OH 的形成也为 PCT 提供了证据。体外和体内实验均证实,在 NIR-II 激光下,本光疗诊断平台通过 CDT/PCT/PTT 三模态联合治疗具有显著的治疗效果,在给予 dpGCS NCs 和单次 NIR-II 激光照射后,荷瘤小鼠的肿瘤完全抑制。这项工作为使用单一激光进行成像引导癌症治疗的 NIR-II 光疗诊断平台的发展提供了一个独特的范例。

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