Tuning the Cellular Uptake and Retention of Rhodamine Dyes by Molecular Engineering for High-Contrast Imaging of Cancer Cells

Probes allowing high-contrast discrimination of cancer cells and effective retention are powerful tools for the early diagnosis and treatment of cancer. However, conventional small-molecule probes often show limited performance in both aspects. Herein, we report an ingenious molecular engineering strategy for tuning the cellular uptake and retention of rhodamine dyes. Introduction of polar aminoethyl leads to the increased brightness and reduced cellular uptake of dyes, and this change can be reversed by amino acetylation. Moreover, these modifications allow cancer cells to take up more dyes than normal cells (16-fold) through active transport. Specifically, we further improve the signal contrast (56-fold) between cancer and normal cells by constructing activatable probes and confirm that the released fluorophore can remain in cancer cells with extended time, enabling long-term and specific tumor imaging.

Automated summary

In this study, an ingenious molecular engineering strategy was developed to regulate the cellular uptake and retention of rhodamine dyes. Introduction of polar aminoethyl increased the brightness and reduced the cellular uptake of dyes, and this change could be reversed by amino acetylation. Furthermore, these modifications enhanced the uptake of dyes by cancer cells (16-fold) through active transport. By constructing activatable probes, the signal contrast (56-fold) between cancer and normal cells was further improved, and it was confirmed that the released fluorophore could remain in cancer cells for an extended time, enabling long-term and specific tumor imaging.