Ag⁺ ions are a well-known antibacterial agent, and Ag nanoparticles act as a reservoir of these Ag⁺ ions for targeted therapy of bacterial infections. However, there are no tools to effectively trigger and monitor the release of Ag⁺ ions from Ag nanoparticles. Photoacoustic (PA) imaging is an emerging noninvasive imaging tool, and gold nanorods (AuNRs) are an excellent contrast agent for PA imaging. In this work, we developed Au/Ag hybrid nanoparticles by coating AuNRs with silver (Ag), which decreased their photoacoustic signal. The as-prepared, Ag-coated Au nanorods (Au/AgNRs) are stable under ambient conditions, but the addition of ferricyanide solution (1 mM) results in oxidative etching of the silver shell. The PA contrast is simultaneously recovered as the silver is released, and this PA signal offers noninvasive monitoring of localized release of Ag⁺ ions. The released Ag⁺ ions exhibit a strong bactericidal efficacy similar to equivalent free Ag⁺ ions (AgNO₃), and the nanoparticles killed >99.99% of both (Gram-positive) methicillin-resistant Staphylococcus aureus (MRSA, 32 μM Ag⁺ equivalent) and (Gram-negative) Escherichia coli (8 μM Ag⁺ equivalent). The theranostic potential of these nanoparticles was demonstrated in a pilot in vivo study. Mice were inoculated with MRSA and Au/AgNRs were subcutaneously implanted followed by silver etching. There was a 730% increase in the PA signal (p < 0.01) pre- and post-etching, and the bacterial counts in infected tissues of the treated group were reduced by 1000-fold (log CFU/g = 4.15 vs 7.75) versus the untreated control; this treatment efficacy was confirmed with histology. We further showed that these hybrid nanoparticles could release Ag⁺ after stimulation by reactive oxygen species including hydrogen peroxide and peroxynitrite. These hybrid Au/Ag nanoparticles are a useful theranostic agent for the photoacoustic imaging and treatment of bacterial infections.

中文翻译：

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用于细菌感染治疗和光声成像的金/银混合纳米颗粒


Ag ⁺离子是众所周知的抗菌剂，Ag 纳米颗粒充当这些 Ag ⁺离子的储存库，用于细菌感染的靶向治疗。然而，没有工具可以有效地触发和监测Ag纳米颗粒中Ag ⁺离子的释放。光声（PA）成像是一种新兴的非侵入性成像工具，而金纳米棒（AuNR）是PA成像的优异造影剂。在这项工作中，我们通过在 AuNR 上涂上银 (Ag) 来开发 Au/Ag 混合纳米颗粒，从而降低了它们的光声信号。所制备的银包覆金纳米棒 (Au/AgNR) 在环境条件下稳定，但添加铁氰化物溶液 (1 mM) 会导致银壳氧化蚀刻。随着银的释放，PA 对比度同时恢复，并且该 PA 信号可对 Ag ⁺离子的局部释放进行无创监测。释放的 Ag ⁺离子表现出与等效游离 Ag ⁺离子 (AgNO ₃ ) 类似的强大杀菌功效，纳米粒子杀死了 >99.99% 的两种（革兰氏阳性）耐甲氧西林金黄色葡萄球菌（MRSA，32 μM Ag ⁺等效物）和（革兰氏阴性）大肠杆菌（8 μM Ag ⁺等效物）。这些纳米颗粒的治疗诊断潜力在体内试验研究中得到了证明。给小鼠接种 MRSA，并将 Au/AgNR 皮下植入，然后进行银蚀刻。蚀刻前后 PA 信号增加了 730% ( p < 0.01)，治疗组感染组织中的细菌计数减少了 1000 倍（log CFU/g = 4.15 vs 7.75) 与未处理的对照相比；这种治疗效果得到了组织学的证实。我们进一步表明，这些杂化纳米颗粒在受到包括过氧化氢和过氧亚硝酸盐在内的活性氧刺激后可以释放Ag ⁺ 。这些混合金/银纳米颗粒是一种有用的治疗诊断剂，可用于光声成像和细菌感染的治疗。