This paper reports the preparation and application of folic acid-conjugated nitrogen-doped graphene quantum dots (N-GQDs) as a fluorescent diagnostic material for MCF-7 cells of breast cancer. N-GQDs were prepared by a hydrothermal method using citric acid as the carbon source and diethylamine as the nitrogen source. The doping of different amounts of nitrogen content was effectively controlled by diethylamine. As the amount of nitrogen increased, more binding sites on the N-GQDs were supplied to the folic acid. Laser confocal scanning microscopy showed that increased folic acid binding facilitated the recognition of and entry to cancer cells, which made the labeled cells emit a stronger fluorescence and thus the cancer cells could be better detected. Cytotoxicity tests showed that the material was of low cytotoxicity, making it a promising prospect for fluorescent probes.

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Accurate distinguish of cancer cells through fluorescence plays an important role in cancer diagnosis. Here we synthesized a blue fluorescent nitrogen-doped graphene quantum dots (N-GQDs) from citric acid and diethylamine via one-step hydrothermal synthesis method which was simple and quick to avoid by-products, and highlighted the binding sites to achieve precise combination. Due to the nitrogen element doping, amide II bond was amply obtained and abundant binding sites were provided for hyaluronic acid (HA) conjugation. N-GQDs solution with different pH value was then conjugated to HA via an amide bond for the recognition of human breast cancer cells (MCF-7 cells), and the formation of amide bond was more favorable under alkaline conditions. HA conjugated N-GQDs (HA-N-GQDs) were combined with CD44 which was over expressed on the surface of MCF-7 cells, resulting in MCF-7 cells performing stronger fluorescence. HA-N-GQDs showed high fluorescence, low toxicity, and good cytocompatibility, which held it play a role in fluorescence imaging for accurate identification of cancer cells.

The nitrogen-doped graphene quantum dot conjugated indomethacin (N-GQD-IDM) was synthesized by an amide reaction. The results of FTIR indicated that the synthesis of N-GQD-IDM was successful. It was then co-cultured with MCF-7 cells, and obvious fluorescence was observed under a laser confocal scanning microscope. With the increase of incubation time, the material accumulated significantly in the cells and the fluorescence intensity of the cells was slightly improved. This compound could be suggested as a promising fluorescent probe in cancer cell labeling.

To imitate the composition of natural bone and further improve the biological property of the materials, ZnO/hydroxyapatite/chitosan-polyethylene oxide@gelatin (ZnO/HAP/CS-PEO@GEL) composite scaffolds were developed. The core-shell structured chitosan-polyethylene oxide@gelatin (CS-PEO@GEL) nanofibers which could form the intramolecular hydrogen bond and achieve an Arg-Gly-Asp (RGD) polymer were first prepared by coaxial electrospinning to mimic the extracellular matrix. To further enhance biological activity, hydroxyapatite (HAP) was grown on the surface of the CS-PEO@GEL nanofibers using chemical deposition and ZnO particles were then evenly distributed on the surface of the above composite materials using RF magnetron sputtering. The SEM results showed that chemical deposition and magnetron sputtering did not destroy the three-dimensional architecture of materials, which was beneficial to cell growth. The cell compatibility and proliferation of MG-63 cells on ZnO/HAP/CS-PEO@GEL composite scaffolds were superior to those on CS-PEO@GEL and HAP/CS-PEO@GEL composite scaffolds. An appropriate amount of ZnO sputtering could promote the adhesion of cells on the composite nanofibers. The structure of bone tissue could be better simulated both in composition and in the microenvironment, which provided a suitable environment for cell growth and promoted the proliferation of MG-63 cells. The biomimetic ZnO/HAP/CS-PEO@GEL composite scaffolds were promising materials for bone tissue engineering.