Li Xingchen, Hao Ming, Liu Annan, Li Lei, Nešić Maja D, Yang Bai, Liu Weiwei, Lin Quan
State Key Laboratory of Supramolecular Structure and Material, College of Chemistry, Jilin University, Changchun 130012, China.
Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Jilin University, Changchun 130021, China; Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, China.
Acta Biomater. 2024 Dec;190:476-487. doi: 10.1016/j.actbio.2024.10.018. Epub 2024 Oct 12.
Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the head and neck region, and its treatment is limited by hypoxia and inadequate oxygen supply. Continuous oxygen delivery combined with photodynamic therapy (PDT) is the key to addressing this issue. Here, a dual-enzyme activity sea urchin-like Au@Pt-Ce6-HN-1 nanoplatform was designed to serve as an "oxygen pump" to alleviate tumor hypoxia for synergistic photodynamic/photothermal therapy (PTT). In this design, the photosensitizer chlorin e6 (Ce6) is covalently linked to the Au@Pt nanozyme for PDT treatment. The Au@Pt nanozyme exhibits catalase-like activity, continuously decomposing HO in the tumor microenvironment to enhance O levels, thereby achieving efficient PDT. Furthermore, Au@Pt can perform PTT and increase oxygen levels under NIR-II light to further promote PDT. The Au@Pt nanozyme also exhibits peroxidase-like activity, generating ·OH for chemodynamic therapy (CDT). Additionally, HN-1 guides the direction of "sniping" OSCC, and its high specificity benefits Au@Pt-Ce6-HN-1 at the tumor site. Au@Pt-Ce6-HN-1 exhibits bright fluorescence (FL), strong CT signal, and photothermal imaging capabilities, laying the foundation for subsequent guided PDT/PTT. This nanoplatform, which combines advantages such as continuous oxygen production, tumor targeting, and multimodal imaging, is expected to provide valuable insights into the treatment of OSCC. STATEMENT OF SIGNIFICANCE: Accurate clinical diagnosis and treatment of OSCC are challenging. We report a dual-enzyme activity sea urchin-like Au@Pt-Ce6-HN-1 nanoplatform, serving as an "oxygen pump" to guide photodynamic therapy (PDT) and photothermal therapy (PTT) for OSCC. This nanoplatform targets OSCC for preoperative CT diagnosis and offers fluorescence visualization for surgical navigation, demonstrating potential in clinical cancer detection and surgery guidance. This innovative approach addresses OSCC hypoxia and enhances treatment efficacy through continuous oxygen production, tumor targeting, and multimodal imaging, significantly improving patient outcomes in OSCC treatment.
口腔鳞状细胞癌（OSCC）是头颈部最常见的恶性肿瘤，其治疗受到缺氧和供氧不足的限制。持续输氧联合光动力疗法（PDT）是解决这一问题的关键。在此，设计了一种具有双酶活性的海胆状Au@Pt-Ce6-HN-1纳米平台，作为“氧泵”来缓解肿瘤缺氧，以进行协同光动力/光热疗法（PTT）。在该设计中，光敏剂二氢卟吩e6（Ce6）与Au@Pt纳米酶共价连接用于PDT治疗。Au@Pt纳米酶具有过氧化氢酶样活性，可在肿瘤微环境中持续分解H₂O₂以提高O₂水平，从而实现高效的PDT。此外，Au@Pt可进行PTT并在近红外二区光下提高氧水平以进一步促进PDT。Au@Pt纳米酶还具有过氧化物酶样活性，产生·OH用于化学动力学疗法（CDT）。此外，HN-1引导“狙击”OSCC的方向，其高特异性有利于Au@Pt-Ce6-HN-1在肿瘤部位发挥作用。Au@Pt-Ce6-HN-1具有明亮的荧光（FL）、强烈的CT信号和光热成像能力，为后续的引导性PDT/PTT奠定了基础。这种结合了持续产氧、肿瘤靶向和多模态成像等优点的纳米平台，有望为OSCC的治疗提供有价值的见解。重要意义声明：OSCC的准确临床诊断和治疗具有挑战性。我们报道了一种具有双酶活性的海胆状Au@Pt-Ce6-HN-1纳米平台，作为“氧泵”来引导OSCC的光动力疗法（PDT）和光热疗法（PTT）。这种纳米平台靶向OSCC用于术前CT诊断，并为手术导航提供荧光可视化，在临床癌症检测和手术引导方面显示出潜力。这种创新方法通过持续产氧、肿瘤靶向和多模态成像解决了OSCC缺氧问题并提高了治疗效果，显著改善了OSCC治疗中的患者预后。
