Nucleotide-derived theranostic nanodots with intrinsic fluorescence and singlet oxygen generation for bioimaging and photodynamic therapy

Abstract

Nucleic acids are important molecules of life and have recently emerged as important functional materials to synthesize, organize and assemble inorganic nanoparticles for various technological applications. In this study, we have systematically investigated the four basic nucleotides of DNA as precursors to form fluorescent nucleotide derived biodots (N-dots) with unique singlet oxygen generation properties by one-pot hydrothermal synthesis. It has been discovered for the first time that the nitrogenous base adenine accounts for the bright fluorescence, while the sugar and phosphate groups of the nucleotide endow the N-dots with good photo-stability. Among the N-dots synthesized in this study, adenosine triphosphate (ATP)-dots were found to exhibit the highest fluorescence quantum yield (QY) of 13.9%, whereas adenosine diphosphate (ADP)-dots exhibited the best photo-stability maintaining 97.6% photoluminescence intensity after continuous UV excitation for 30 min. Overall, deoxyadenosine monophosphate (dAMP)-dots display both high fluorescence QY (12.4%) and good photo-stability (91.9%). Most critically, dAMP-dots show the highest singlet oxygen generation with a remarkable singlet oxygen (¹O₂) quantum yield of 1.20 surpassing the ¹O₂ quantum yield of the conventional photosensitizer Rose Bengal (0.75). Further cellular experiments reveal that dAMP-dots possess excellent cellular uptake ability for successful fluorescent labeling with the ability to kill >60% HeLa cancer cells under white light treatment within 10 minutes. Additionally, N-dots possess excellent stability against both UV irradiation and DNase enzymatic action. These results demonstrate the unique physiochemical properties of N-dots, including an ultra-small size for cellular uptake, tunable photoluminescence for bioimaging, excellent aqueous solubility, high chemical stability and photo-stability as well as excellent singlet oxygen quantum yield with inherent biocompatibility for photodynamic therapy, which are important factors contributing to the promising theranostic applications in future personalized nanomedicine.