Folic acid-functionalized polymer dots encapsulating deep red fluorescent carbon nanodots for specific imaging of folate-receptor-positive cancer cells.

Cancer metastasis represents one of the greatest challenges in oncology, as it significantly raises the risk of mortality from the disease. Consequently, the development of techniques for early tumor detection and quantification is of critical importance. In this study, we developed folic acid (FA) functionalized water-soluble polymer dots encapsulating deep red fluorescent carbon nanodots (CDs) for specific in vivo tumor imaging. Deep red fluorescent CDs, with an emission peak at 673 nm and a fluorescence quantum yield of 11.6% in ethanol, were facilely synthesized from peach blossoms using a microwave-assisted method. Further characterization revealed that the prepared CDs exhibited negligible fluorescence in aqueous media. To enable the use of CDs for specifically imaging cancer cells and tumors in mice, we self-assembled them with amphiphilic FA-modified polymer, DSPE-PEG-FA, to generate polymer nanodots (FA-dots). The resulting FA-dots, with an average particle size of 79 nm and a fluorescence quantum yield of 10.3%, demonstrated excellent stability and low cytotoxicity, allowing efficient discrimination between FR-positive HeLa cells and FR-negative cancer cells or normal cells. Additionally, owing to their strong absorption in the deep red region (with a maximum absorption at 665 nm), FA-dots could also serve as a photoacoustic imaging agent. Furthermore, FA-dots were capable of visualizing tumors in vivo within an established orthotopic HeLa model in mice.