Highly fluorescent N-doped carbon dots with two-photon emission for ultrasensitive detection of tumor marker and visual monitor anticancer drug loading and delivery

Early diagnosis and therapy are practically important to effectively prevent cancer and improve patients’ life quality. Herein, a simple and sensitive two-photon imaging fluorescent nitrogen-doped carbon dots (N-CDs) platform was constructed to detect β-glucuronidase (βG, a tumor-invasive biomarker) based on inner filter effect (IFE), to visually monitor anticancer drug loading by fluorescence resonance energy transfer (FRET), and to effectively treat cancer by chemotherapy. To build this sensing platform, novel N-CDs with strong green emission (Ca. QY = 45%) were synthesized by one-pot pyrolysis reaction, and specifically, careful structure design of the excitation bands of N-CDs well covered the absorption bands of p-nitrophenol (PNP, βG catalytic product), making it ultra-sensitive towards the activity of βG and showing good linear relationship from 1 to 15 U/L and exciting detection limit of 0.3 U/L (S/N = 3). This sensing platform has been successfully employed for βG sensing in both human serum and intracellular detection. Moreover, we also demonstrated the first application of N-CDs as a novel visual detection sensor to monitor the loading process of doxorubicin, and as a nanocarrier for cancer therapy. More importantly, the N-CDs also exhibited high quality single- and two-photon fluorescence in high depth (18 μm), enabling the N-CDs to real-time monitor the endocytosis, intracellular distribution and release of drugs, indicating significant potential for biomedicine and bioimaging applications.