Abstract:
Accurate fluorescence imaging of nanocarriers in vivo remains a challenge owing to interference derived mainly from biological tissues and free probes. To address both issues, the current study explored fluorophores in the near-infrared (NIR)-II window with aggregation-caused quenching (ACQ) properties to improve imaging accuracy. Candidate fluorophores with NIR-II emission, ACQ984 (λem = 984 nm) and IR-1060 (λem = 1060 nm), from the aza-BODIPY and cyanine families, respectively, were compared with the commercial fluorophore ICG with NIR-II tail emission and the NIR-I fluorophore P2 from the aza-BODIPY family. ACQ984 demonstrates high water sensitivity with complete fluorescence quenching at a water fraction greater than 50%. Physically embedding the fluorophores illuminates various nanocarriers, while free fluorophores cause negligible interference owing to the ACQ effect. Imaging based on ACQ984 revealed fine structures in the vascular system at high resolution. Moreover, good in vivo and ex vivo correlations in the monitoring of blood nanocarriers can be established, enabling real-time noninvasive in situ investigation of blood pharmacokinetics and dynamic distribution in various tissues. IR-1060 also has a good ACQ effect, but the lack of sufficient photostability and steady post-labeling fluorescence undermines its potential for nanocarrier bioimaging. P2 has an excellent ACQ effect, but its NIR-I emission only provides nondiscriminative ambiguous images. The failure of the non-ACQ probe ICG to display the biodistribution details serves as counterevidence for the improved imaging accuracy by NIR-II ACQ probes. Taken together, it is concluded that fluorescence imaging of nanocarriers based on NIR-II ACQ probes enables accurate in vivo bioimaging and real-time in situ pharmacokinetic analysis.
摘要:
由于主要来自生物组织和游离探针的干扰,体内纳米载体的精确荧光成像仍然是一个挑战。为了解决这两个问题,当前的研究探索了近红外(NIR)-II窗口中具有聚集引起的猝灭(ACQ)特性的荧光团,以提高成像精度。具有NIR-II发射的候选荧光团,ACQ984(λem=984nm)和IR-1060(λem=1060nm),来自aza-BODIPY和花青家族,分别,与具有NIR-II尾发射的商业荧光团ICG和来自aza-BODIPY家族的NIR-I荧光团P2进行了比较。ACQ984证明了在大于50%的水分数下具有完全荧光猝灭的高水敏感性。物理嵌入荧光团照亮各种纳米载体,而游离荧光团由于ACQ效应而引起的干扰可忽略不计。基于ACQ984的成像显示了高分辨率的血管系统中的精细结构。此外,在血液纳米载体的监测中可以建立良好的体内和离体相关性,能够对各种组织中的血液药代动力学和动态分布进行实时非侵入性原位研究。IR-1060还具有良好的ACQ效果,但是缺乏足够的光稳定性和稳定的标记后荧光破坏了其纳米载体生物成像的潜力。P2具有优异的ACQ效果,但它的NIR-I发射只提供了无区别的模糊图像。非ACQ探针ICG无法显示生物分布细节,这与NIR-IIACQ探针提高的成像精度相反。一起来看,结论是基于NIR-IIACQ探针的纳米载体的荧光成像能够实现准确的体内生物成像和实时原位药代动力学分析。