In Situ Radical Reaction‐Modified Carbon Dot Nanocapsules with Macrophage Escape and Prolonged Imaging

Carbon dots (CDs) have emerged as an extremely promising platform for biological imaging, owing to their optical properties and low toxicity. However, one of the major challenges in utilizing CDs for in vivo imaging is their high immunogenicity and rapid clearance, which limits their potential. Herein, a novel approach for mitigating these issues is presented through the development of carbon dot nanocapsules (nCDs). Specifically, CDs are encapsulated within a zwitterionic polymer shell composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) to create nCDs with a size of ≈40 nm. Notably, the nCDs exhibit excitation-dependent photoluminescence behavior in the range of 550-600 nm, with tunability based on the excitation wavelength. In confocal imaging, CDs display a strong fluorescence signal after 8 h of incubation with phagocytes, while nCDs show minimal signal, suggesting that nCDs may be capable of evading phagocyte uptake. Furthermore, imaging studies in zebrafish demonstrate that nCDs exhibit a retention time >10 times longer than that of CDs, with fluorescence intensity remaining at 81% after 10 h compared to only 8% for CDs. Taken together, the study presents a novel approach for enhancing the performance of CDs in in vivo imaging applications, offering significant potential for clinical translation.