Aluminum salts are crucial ingredients in vaccine formulations. These salts work as adjuvants, enhancing the immune system's response to an antigen. However, aluminum salt dosages have been limited due to their possible side effects associated with neurological disorders such as Alzheimer’s, Parkinson’s, and multiple sclerosis. Current vaccines also lack imaging modalities with high spatiotemporal resolution needed to visualize the dynamic response of the immune system at the vaccination site and nearby lymph nodes. To address these shortcomings, in this work, we have developed highly biocompatible aluminum-doped graphene quantum dots (Al-GQDs) as potential adjuvant delivery vehicles with dual-mode fluorescence and ultrasound imaging capabilities. Nanometer-sized (<5 nm) Al-GQDs are biocompatible (up to 80% cell viability) in HeK293 cells at a staggeringly high concentration of 11.2 mg/mL, which is uncommon for nanomaterials. Their structural and chemical features assessed via the FTIR and EDS include a graphitic core with functional groups that are amenable to covalent and noncovalent bonding with molecules for therapeutic applications. Moreover, they also exhibit fluorescence in the visible and near-infrared regions with a pH-dependent response suitable for cellular environment pH sensing. The fluorescence and ultrasound tracking capabilities of Al-GQDs are demonstrated in vitro and in tissue phantoms (agarose gel, vascular phantom, and animal tissue). Al-GQDs internalize and accumulate at a maximum of 24 h in cells and enhance the ultrasound signal in biological environments. Given their pH-dependent fluorescence and ultrasound imaging capabilities, biocompatible Al-GQDs developed for the first time in this work present a unique alternative to current Al-based adjuvants, enabling high-depth ultrasound and high-precision fluorescence tracking as well as sensing and delivery capabilities. Such a multifunctional adjuvant-inspired system is intended to further complement and aid rapidly advancing vaccine research and development.

中文翻译：

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用于双模态荧光和超声成像应用的生物相容性掺铝石墨烯量子点

铝盐是疫苗配方中的关键成分。这些盐作为佐剂，增强免疫系统对抗原的反应。然而，铝盐的剂量由于其可能与阿尔茨海默病、帕金森病和多发性硬化症等神经系统疾病相关的副作用而受到限制。目前的疫苗还缺乏高时空分辨率的成像方式，无法可视化免疫系统在疫苗接种部位和附近淋巴结的动态反应。为了解决这些缺点，在这项工作中，我们开发了高度生物相容性的铝掺杂石墨烯量子点（Al-GQD）作为具有双模式荧光和超声成像功能的潜在佐剂输送载体。纳米尺寸 (<5 nm) Al-GQD 在 HeK293 细胞中具有生物相容性（高达​​ 80% 的细胞活力），浓度高达 11.2 mg/mL，这对于纳米材料而言并不常见。通过 FTIR 和 EDS 评估其结构和化学特征，包括带有官能团的石墨核心，这些官能团适合与分子进行共价和非共价键合，用于治疗应用。此外，它们还在可见光和近红外区域表现出荧光，具有适合细胞环境 pH 感测的 pH 依赖性响应。Al-GQD 的荧光和超声跟踪能力在体外和组织模型（琼脂糖凝胶、血管模型和动物组织）中得到了证明。Al-GQDs 在细胞内内化和积累最多 24 小时，并增强生物环境中的超声信号。鉴于其 pH 依赖性荧光和超声成像能力，这项工作中首次开发的生物相容性 Al-GQD 为当前基于 Al 的佐剂提供了一种独特的替代品，可实现高深度超声和高精度荧光跟踪以及传感和检测。交付能力。这种多功能佐剂系统旨在进一步补充和帮助快速推进疫苗研究和开发。