A Short Biography of Carbon Dots

Carbon dots (CDs) are a new type of zero-dimensional fluorescent nanomaterials with a size of less than 10 nm, which are composed of a graphitized sp2 carbon core and a shell containing abundant groups such as amino groups, ether groups, carbonyl groups, and hydroxyl groups on the surface, has the advantages of easy preparation, low toxicity, stable optical properties and no photobleaching. Since its discovery in 2004, the preparation, luminescence mechanism and application of CDs have been the hotspot of research. CDs preparation methods are divided into top-down and bottom-up methods, covering electrochemical oxidation, laser ablation, hydrothermal, pyrolysis, and microwave methods. Hydrothermal and microwave methods are favored by simple and fast due to their simplicity and speed. At present, there is no unified explanation for the luminescence mechanism of CDs, and there are three widely accepted ones: 1, the fluorescence effect of quantum confinement and conjugated π bond structure determined by the carbon core structure; 2, Determined by the surface chemical groups; 3, The theory of molecular states determined by fluorescent molecular groups.

CDs can be divided into biomass-based CDs and non-biomass-based CDs according to their sources. The carbon source of the former is biomass materials, such as plants, animals and their wastes; the carbon source of the latter is chemical reagents, such as citric acid, p-phenylenediamine, etc. Compared with chemical reagents, biomass materials exist widely in nature, are rich in variety and can be regenerated repeatedly, so biomass-based CDs have attracted more and more attention of scientists.

Application of Carbon Dots in Biomedicine

CDs have the advantages of high luminous efficiency, stable optical properties, good biocompatibility, easy preparation, and adjustable color, so they have a wide range of applications in many fields.

Bioimaging

Since CDs were proven to be used for in vivo and in vitro imaging in 2007, biomass-based CDs have become ideal materials for nanobioimaging in the biological field due to their good biocompatibility and excellent photostability. The researchers used CDs prepared from orange juice to image human osteosarcoma cells (MG-63), which clearly showed the aggregation of green fluorescent carbon nanoparticles in the cells, and the nucleus region could be clearly observed. Other researchers studied the distribution of CDs made from spider silk in cells and found that only CDs were present in the cytoplasm, while no traces of CDs were found in mitochondria and endosomes. However, some scholars have found that CDs formed from hydrothermally carbonized petals can enter the cytoplasm and nucleus of human cervical squamous cell carcinoma cells (A193) through endocytosis. The current research progress is still difficult to elucidate the selective phagocytosis mechanism of CDs by different organelles.

In nature, there are many autofluorescence phenomena in biological tissues, and the autofluorescence range is mostly concentrated in the blue light region. For blue-green light CDs, the interference of this biological tissue autofluorescence is often unavoidable. In addition, blue-green fluorescence also has shortcomings such as shallow penetration depth when applied to biological imaging. Therefore, in recent years, CDs used for biological imaging have mostly focused on red or near-infrared luminescence imaging and two-photon imaging. The researchers prepared CDs from watermelon juice, and based on the CDs, they developed a near-infrared second region (NIR-II)-based CDs nanoprobe excited at 808 nm, and realized in vivo NIR-II bioimaging. It is proved that the clearance rate of CDs in the kidney is very fast. In addition, the designed nanoprobe also has a high photothermal efficiency (30.6%), making it an ideal material for thermal ablation of cancer.

Drug Delivery

In recent years, CDs have attracted much attention in tumor drug therapy due to their large specific surface area and abundant functional groups. It is often used as a nano-diagnostic platform integrating optical imaging and drug therapy to achieve controlled release of drugs guided by luminescence imaging, thereby improving the therapeutic effect of drugs and avoiding the damage of drugs to other organs. The researchers used milk as raw material to synthesize CDs by hydrothermal method, and used multiple functional groups on their surface to combine with doxorubicin (DOX) through electrostatic interaction to construct a drug-controlled release system, which exhibited pH-dependent release behavior. Compared with free DOX, CDs-DOX complexes were more destructive to adenoid cystic carcinoma cell lines, but less toxic to mouse fibroblast cell line (L929). And the CDs-DOX complex improves the efficiency of cancer treatment by localizing more drugs in the nucleus of tumor cells and inducing a higher apoptosis rate of ACC-2 cells. Other researchers proposed another pH-based drug delivery system. They prepared biomass CDs with narrow size distribution and tunable optical properties by using black tea as raw material through HNO3 oxidation. It can label subcellular structures, escape detection by lysosomes, and distribute itself into the cytoplasm, releasing DOX as a free drug in the lower pH tumor microenvironment. The high biocompatibility and large specific surface area of ​​biomass-based CDs can enhance cellular absorption, which is beneficial to the combination with therapeutic drugs, and is an excellent carrier for drug delivery. The strong selectivity of drug delivery systems is crucial for improving local therapeutic efficacy and reducing side effects in non-infectious and non-cancerous tissues, providing a new idea for cancer treatment.

Sensing

CDs have the characteristics of adjustable fluorescence, good stability, good water solubility, and easy surface functionalization. They can effectively capture target analytes, and can realize ions, molecules (such as thrombin, hyaluronidase, glyphosate), antibiotics (Sensing detection of tetracycline) concentration, ambient temperature or pH value, etc., has the characteristics of simple operation and visualization.