A NIR-II-emitting gold nanocluster-based drug delivery system for smartphone-triggered photodynamic theranostics with rapid body clearance
A NIR-II-emitting gold nanocluster-based drug delivery system for smartphone-triggered photodynamic theranostics with rapid body clearance
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DOI：
10.1016/j.mattod.2021.09.022
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发表时间：
2021-12-15
期刊：
影响因子：
24.2
通讯作者：
Wu, Mei X.
中科院分区：
文献类型：
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作者：
Kong, Yifei;Santos-Carballal, David;Wu, Mei X.
纳米医学在结构上变得复杂，以便一次执行多项任务。然而，翻译研究的可靠性、一致性和可重复性不尽如人意，是翻译研究中流失率高的主要原因。到目前为止，大多数研究都片面地关注无机纳米粒子作为癌症治疗剂的治疗效果，但忽视了它们从体内的消除-这是获得监管批准的关键因素。因此，我们没有开发在医学实践中具有不确定未来的新药物纳米载体，而是选择利用有前途和可平移的金纳米簇（AuNC）的效用来设计简单但稳健的“一体化”纳米簇药物递送系统，其中AuNC不仅加强中性红（NR）作为模型药物的肾清除，而且还通过增强的渗透性和保留（EPR）效应辅助其被动肿瘤靶向。更有趣的是，NR可以刺激活性氧（ROS）的产生，从而在智能手机手电筒的超低辐射下抑制肿瘤生长（注量率：8 mW/cm（2））。这一发现对于缺乏医疗资源的低收入和中等收入国家尤其有价值。通过第一性原理模拟，我们还深入研究了在第二近红外窗口（NIR-II，1000-1700 nm）发射的AuNCs的能量，结构和电子性质。简而言之，我们的模型满足了转化开发的安全性、有效性和成本效益要求。
Nanomedicine has grown structurally complex in order to perform multiple tasks at a time. However, their unsatisfied reliability, uniformity and reproducibility account for the high rates of attrition in translational research. So far, most studies have been one-sidedly focused on the treatment efficacy of inorganic nanoparticles as cancer therapeutics, but overlook their elimination from the body - a key factor in getting regulatory approval. Instead of developing a new drug nanocarrier with uncertain future in medical practice, we therefore choose to leverage the utility of promising and translatable gold nanoclusters (AuNCs) for designing a simple but robust "all-in-one" nanocluster drug delivery system, where the AuNCs not only strengthen the renal clearance of neutral red (NR) as a model drug, but also aid its passive tumor targeting via the enhanced permeability and retention (EPR) effect. More interestingly, NR can stimulate the production of reactive oxygen species (ROS) to suppress tumor growth under ultralow-level radiation with a smartphone's torch (fluence rate: 8 mW/cm(2)). This finding is especially valuable to low-and middle-income countries lacking resources in healthcare settings. By means of first-principles simulations, we also study in-depth the energies, structural and electronic properties of the AuNCs emitting in the second near-infrared window (NIR-II, 1000-1700 nm). In brief, our model fulfills safety, effectiveness and cost-effectiveness requirements for translational development.