Facile Alkyne Assembly-Enabled Functional Au Nanosheets for Photoacoustic Imaging-Guided Photothermal/Gene Therapy of Orthotopic Glioblastoma

IF 14.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of the American Chemical Society Pub Date : 2024-11-20 DOI:10.1021/jacs.4c08990

Xixi Hu, Peiling Li, Dongdong Xu, Hua Liu, Qiaoqiao Hao, Mengyang Zhang, Zhaoyin Wang, Tianxiang Wei, Zhihui Dai

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Abstract

Treatment of glioblastoma (GBM) remains challenging due to the presence of blood–brain barrier (BBB) and tumor heterogeneity. Herein, Au nanosheets (AuNSs) functionalized with RGD peptides and small interfering RNA (siRNA), referred to as AuNSs-RGD-C≡C-siRNA (ARCR), are prepared to achieve multimodal therapy for GBM. The AuNSs with a large modifiable surface area, intriguing photothermal conversion efficiency (50.26%), and remarkable photothermal stability (44 cycles over 7 h) are created using a well-designed amphiphilic surfactant. Furthermore, alkynyl groups are assembled onto the Au surface within 1 min, enabling strong covalent binding of siRNA to AuNSs and thereby avoiding the interference from biological thiols. Owing to the lipophilicity of the surfactant and the targeting property of RGD, ARCR effectively passes through the BBB and accumulates in GBM tumor regions, allowing near-infrared photoacoustic imaging-guided photothermal/gene therapy. This work proposes a facile strategy to construct theranostic Au-based materials, highlighting the potential of multifunctional nanoagents for GBM therapy.

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用于光声成像引导的直位胶质母细胞瘤光热/基因治疗的简易炔烃组装功能金纳米片

由于存在血脑屏障（BBB）和肿瘤异质性，胶质母细胞瘤（GBM）的治疗仍然充满挑战。本文制备了具有RGD肽和小干扰RNA（siRNA）功能的金纳米片（AuNSs），称为AuNSs-RGD-C≡C-siRNA（ARCR），以实现对GBM的多模式治疗。利用精心设计的两亲性表面活性剂制备的 AuNSs 具有较大的可修饰表面积、引人入胜的光热转换效率（50.26%）和显著的光热稳定性（7 小时内可循环 44 次）。此外，炔基团可在 1 分钟内组装到金表面，从而实现 siRNA 与 AuNSs 的强共价结合，避免了生物硫醇的干扰。由于表面活性剂的亲脂性和 RGD 的靶向性，ARCR 能有效穿过 BBB 并在 GBM 肿瘤区域聚集，从而实现近红外光声成像引导的光热/基因治疗。这项研究提出了一种构建金基治疗材料的简便策略，凸显了多功能纳米试剂在 GBM 治疗中的潜力。

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来源期刊

Journal of the American Chemical Society 化学-化学综合

CiteScore

24.40

自引率

6.00%

发文量

2398

审稿时长

1.6 months

期刊介绍： The flagship journal of the American Chemical Society, known as the Journal of the American Chemical Society (JACS), has been a prestigious publication since its establishment in 1879. It holds a preeminent position in the field of chemistry and related interdisciplinary sciences. JACS is committed to disseminating cutting-edge research papers, covering a wide range of topics, and encompasses approximately 19,000 pages of Articles, Communications, and Perspectives annually. With a weekly publication frequency, JACS plays a vital role in advancing the field of chemistry by providing essential research.