Red Fluorescent Carbon Quantum Dots for Diagnosis of Acidic Microenvironment in Tumors

Cancer remains a major global cause of morbidity and mortality. Diagnosis at an early stage can significantly improve the survival of cancer patients. Cancers of different origins often have vastly different genotypes and phenotypes. Therefore, it is challenging to establish a universal strategy for cancer detection. Universal cancer detection can be potentially achieved by using pH-responsive probes. An acidic microenvironment is mainly caused by lactic acid accumulation in rapidly growing tumor cells. Based on the difference in pH between tumor and normal tissues, fluorescent materials that respond to a pH of around 6.8 are ideal for tumor detection. Carbon quantum dots (CQDs) have attracted much attention in bioimaging owing to their outstanding characteristics such as stable photoluminescence, low cytotoxicity, excellent biocompatibility, and resistance to photobleaching. In this study, red fluorescent CQDs (R-CQDs) were synthesized by the solvothermal treatment of 4-(dimethylamino) phenol in the presence of potassium periodate. The UV Vis spectrum of the R-CQDs showed a characteristic absorption peak at 545 nm. The photoluminescence spectrum revealed an emission peak at 640 nm. The brightness of this photoluminescence peak was quantified to be 12.8% in terms of the absolute quantum yield (QY). Transmission electron microscopy (TEM) images showed that the R-CQDs have uniform sizes with an average diameter of 4 nm and a lattice spacing of 0.21 nm. Fourier transform infrared (FT-IR) spectroscopy and X-ray photoelectron spectroscopy (XPS) confirmed that the R-CQDs have a large number of carboxyl groups. The Raman spectrum of the R-CQDs showed the characteristic D band at 1340 cm(-1) and G band at 1585 cm(-1). The X-ray powder diffraction (XRD) pattern showed a broad (002) peak centered at around 23 degrees. The R-CQDs were responsive to highly acidic or alkaline conditions. The incorporation of a block copolymer (MeO-PEG-PDPA), prepared by atom transfer radical polymerization (ATRP), on the R-CQDs produced pH-responsive fluorescent CQDs (pRF-R-CQDs). Photoluminescence (PL) spectra showed that the pRF-R-CQDs were responsive at pH 6.8. At pH > 6.8, the fluorescence of the pRF-R-CQDs would be quenched because of deprotonation of the amine groups. In contrast, protonation of the amine groups would lead to a dramatic increase in fluorescence emission. TEM images showed that the pRF-R-CQDs self-assemble and disassemble at pH 6.8 because of their pH-responsive properties. Compared with most existing fluorescent materials, the pRF-R-CQDs can effectively resist photobleaching and autofluorescence. Moreover, these pRFR-CQDs have minimal toxicity and can distinguish tumors from normal tissues. Therefore, pRF-R-CQDs have great potential for use as a universal material in tumor microenvironment diagnosis.

Automated summary

Cancer remains a major global cause of morbidity and mortality, and early diagnosis is crucial for improving the survival of cancer patients. Establishing a universal strategy for cancer detection is challenging due to the vast differences in genotypes and phenotypes of cancers. However, using pH-responsive probes may potentially achieve universal cancer detection, particularly in acidic microenvironments caused by lactic acid accumulation in tumor cells.