Contrast enhancement in optoacoustic (photoacoustic) imaging can be achieved with agents that exhibit high absorption cross-sections, high photostability, low quantum yield, low toxicity, and preferential bio-distribution and clearance profiles. Based on advantageous photophysical properties of croconaine dyes, we explored croconaine-based nanoparticles (CR780RGD-NPs) as highly efficient contrast agents for targeted optoacoustic imaging of challenging preclinical tumor targets. Initial characterization of the CR780 dye was followed by modifications using polyethylene glycol and the cancer-targeting c(RGDyC) peptide, resulting in self-assembled ultrasmall particles with long circulation time and active tumor targeting. Preferential bio-distribution was demonstrated in orthotopic mouse brain tumor models by multispectral optoacoustic tomography (MSOT) imaging and histological analysis. Our findings showcase particle accumulation in brain tumors with sustainable strong optoacoustic signals and minimal toxic side effects. This work points to CR780RGD-NPs as a promising optoacoustic contrast agent for potential use in the diagnosis and image-guided resection of brain tumors.

使用具有高吸收截面，高光稳定性，低量子产率，低毒性以及优先的生物分布和清除特性的试剂可以实现光声（光声）成像的对比度增强。基于藏红花染料的光物理特性，我们探索了基于藏花红素的纳米颗粒（CR780RGD-NPs）作为高效的造影剂，可用于挑战性临床前肿瘤靶标的靶向光声成像。CR780染料的初始表征之后，是使用聚乙二醇和靶向癌的c（RGDyC）肽进行修饰，从而产生了具有长循环时间和活性靶向肿瘤的自组装超小颗粒。通过多光谱光声层析成像（MSOT）成像和组织学分析，在原位小鼠脑肿瘤模型中证明了优先的生物分布。我们的发现表明，脑肿瘤中的颗粒蓄积具有可持续的强光声信号，且毒性副作用最小。这项工作指出CR780RGD-NPs是一种有前途的光声造影剂，可用于脑肿瘤的诊断和图像引导切除。