| Autor: |
East AK; 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., Lee MC; 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., Jiang C; 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., Sikander Q; 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., Chan J; 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. |
| Abstrakt: |
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. |
