Department of Chemistry, Beckman Institute for Advanced Science and Technology, and Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
J Am Chem Soc. 2023 Apr 5;145(13):7313-7322. doi: 10.1021/jacs.2c13489. Epub 2023 Mar 27.
The attachment of glucose to drugs and imaging agents enables cancer cell targeting via interactions with GLUT1 overexpressed on the cell surface. While an added benefit of this modification is the solubilizing effect of carbohydrates, in the context of imaging agents, aqueous solubility does not guarantee decreased π-stacking or aggregation. The resulting broadening of the absorbance spectrum is a detriment to photoacoustic (PA) imaging since the signal intensity, accuracy, and image quality all rely on reliable spectral unmixing. To address this major limitation and further enhance the tumor-targeting ability of imaging agents, we have taken a biomimetic approach to design a multivalent glucose moiety (mvGlu). We showcase the utility of this new group by developing aza-BODIPY-based contrast agents boasting a significant PA signal enhancement greater than 11-fold after spectral unmixing. Moreover, when applied to targeting cancer cells, effective staining could be achieved with ultra-low dye concentrations (50 nM) and compared to a non-targeted analogue, the signal intensity was >1000-fold higher. Lastly, we employed the mvGlu technology to develop a logic-gated acoustogenic probe to detect intratumoral copper (i.e., Cu(I)), which is an emerging cancer biomarker, in a murine model of breast cancer. This exciting application was not possible using other acoustogenic probes previously developed for copper sensing.
葡萄糖与药物和成像剂结合，通过与细胞表面过表达的 GLUT1 相互作用，实现癌细胞靶向。虽然这种修饰的一个额外好处是碳水化合物的增溶作用，但在成像剂的情况下，水溶解度并不能保证减少 π-堆积或聚集。由此导致的吸收光谱变宽是光声（PA）成像的一个不利因素，因为信号强度、准确性和图像质量都依赖于可靠的光谱解混。为了解决这个主要限制并进一步增强成像剂的肿瘤靶向能力，我们采用了仿生方法来设计多价葡萄糖部分（mvGlu）。我们通过开发基于 aza-BODIPY 的对比剂展示了这个新基团的实用性，这些对比剂在光谱解混后具有超过 11 倍的显著 PA 信号增强。此外，当应用于靶向癌细胞时，即使使用超低的染料浓度（50 nM）也可以实现有效染色，并且与非靶向类似物相比，信号强度高出 1000 多倍。最后，我们利用 mvGlu 技术开发了一种逻辑门控声敏探针，用于在乳腺癌的小鼠模型中检测肿瘤内的铜（即 Cu(I)），这是一种新兴的癌症生物标志物。这一令人兴奋的应用是以前开发用于铜感测的其他声敏探针所不可能实现的。
