State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, People's Republic of China.
ACS Nano. 2022 Nov 22;16(11):19053-19066. doi: 10.1021/acsnano.2c08094. Epub 2022 Nov 9.
The critical role of transition metal dyshomeostasis in Alzheimer's disease (AD) pathology poses demands of imaging for brain copper levels. Nanostructured probes afford prolonged retention time, increased accumulation, and enhanced photostability; however, their development for activatable photoacoustic (PA) imaging remains largely unexplored. We develop a principle of concept for activable PA imaging using cation exchange of ultrathin zinc selenide (ZnSe) nanoplatelets for monitoring brain copper levels in AD mice. We start from quantitative modeling of optical absorption, time-resolved temperature field, and thermal expansion of copper selenide (CuSe) nanocrystals of different morphologies and reveal that ultrathin nanoplatelets afford substantial enhancement of near-infrared (NIR) absorption and PA pressures as compared to nanodots and nanoparticles. By tethering with a blood-brain barrier (BBB)-targeting peptide ligand, the ultrathin ZnSe nanoplatelet probe efficiently transports across the BBB and rapidly exchanges with endogenous copper ions, boosting activatable PA imaging of brain copper levels. We also demonstrate that the efficient exchange of ZnSe nanoplatelets with copper ions can reduce oxidative stress of neurons and protect neuronal cells from apoptosis. The nanoplatelet probe provides a paradigm for activatable PA imaging of brain copper levels, highlighting its potential for pathophysiologic study of AD.
过渡金属动态失衡在阿尔茨海默病（AD）病理学中的关键作用对大脑铜水平的成像提出了要求。纳米结构探针提供了更长的保留时间、增加的积累和增强的光稳定性；然而，它们在可激活光声（PA）成像方面的开发在很大程度上仍未得到探索。我们开发了一种使用超薄膜状硒化锌（ZnSe）纳米板的阳离子交换来监测 AD 小鼠大脑铜水平的可激活 PA 成像原理。我们从不同形态的铜硒（CuSe）纳米晶体的光吸收、时间分辨温度场和热膨胀的定量建模开始，并揭示出与纳米点和纳米颗粒相比，超薄纳米板提供了大量增强的近红外（NIR）吸收和 PA 压力。通过与血脑屏障（BBB）靶向肽配体结合，超薄 ZnSe 纳米板探针能够有效地穿过 BBB 并与内源性铜离子快速交换，从而增强大脑铜水平的可激活 PA 成像。我们还证明，ZnSe 纳米板与铜离子的有效交换可以减少神经元的氧化应激并保护神经元细胞免于凋亡。该纳米板探针为大脑铜水平的可激活 PA 成像提供了范例，突出了其在 AD 病理生理学研究中的潜力。
