Superoxide Anion-Mediated Afterglow Mechanism-Based Water-Soluble Zwitterion Dye Achieving Renal-Failure Mice Detection

Afterglow materials-based biological imaging has promising application prospects, due to negligible background. However, currently available afterglow materials mainly include inorganic materials as well as some organic nanoparticles, which are difficult to translate to the clinic, resulting from non-negligible metabolic toxicity and even leakage risk of inorganic heavy metals. Although building small organic molecules could solve such obstacles, organic small molecules with afterglow ability are extremely scarce, especially with a sufficient renal metabolic capacity. To address these issues, herein, we designed water-soluble zwitterion Cy5-NF with renal metabolic capacity and afterglow luminescence, which relied on an intramolecular cascade reaction between superoxide anion (O₂^•-, instead of ¹O₂) and Cy5-NF to release afterglow luminescence. Of note, compared with different reference contrast agents, zwitterion Cy5-NF not only had excellent afterglow properties but also had a rapid renal metabolism rate (half-life period, t_1/2, around 10 min) and good biocompatibility. Unlike prior afterglow nanosystems possessing a large size, for the first time, zwitterion Cy5-NF has achieved the construction of water-soluble renal metabolic afterglow contrast agents, which showed higher sensitivity and signal-to-background ratio in afterglow imaging than fluorescence imaging for the kidney. Moreover, zwitterion Cy5-NF had a longer kidney retention time in renal-failure mice (t_1/2 more than 15 min). More importantly, zwitterion Cy5-NF can be metabolized very quickly even in severe renal-failure mice (t_1/2 around 25-30 min), which greatly improved biosecurity. Therefore, we are optimistic that the O₂^•--mediated afterglow mechanism-based water-soluble zwitterion Cy5-NF is very promising for clinical application, especially rapid detection of kidney failure.