Research on Metal Nanoclusters in the Field of Biomedicine

Due to the excellent characteristics of metal nanoclusters, they have many applications in the field of biomedicine. Current research shows that metal nanoclusters have good application value in biosensors, nucleic acid and protein molecular detection.

Application of Metal Nanoclusters in Biosensing

Metal nanoclusters have excellent fluorescence and catalytic properties, and are ideal fluorescent and chromatic signal probes. At the same time, the specific interaction between metal nanoclusters and analytes can cause the change of metal cores, ligand shells or the surrounding microenvironment. The change causes a change in performance. Therefore, the metal nanoclusters integrate the identification element and the signal conversion element as a whole, and the biosensor constructed therefrom shows good selectivity and sensitivity.

Nucleic acid Detectionr
Nucleic acids include deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), and their rapid detection and accurate quantification are of great significance for disease diagnosis, identification of harmful pathogens, gene therapy and disease monitoring. Metal nanoclusters synthesized with DNA as template molecules, such as DNA-AgNCs and DNA-CuNCs, have been widely used in the highly sensitive detection of nucleic acids. These metal nanoclusters have excellent characteristics such as controllable size, simple preparation, and variable and adjustable fluorescence. More importantly, the DNA synthesis template can be connected to a nucleic acid aptamer of specific recognition function or a complementary nucleic acid sequence through reasonable design and coding. This part of the functional nucleic acid does not participate in the metal nanocluster, so its molecular recognition function is fully retained. Therefore, such metal nanoclusters can be used as sensor elements to avoid or simplify the chemical modification process of biological recognition nucleic acids during sensor assembly.

Protein Detectionr
Abnormal expression of protein or abnormal protease activity is often closely related to the occurrence and development of specific diseases, so protein is also an important disease biomarker. Aptamer-modified DNA-protected metal nanoclusters can be directly used for the detection of target proteins. For example, researchers connect the DNA synthesis template of CuNCs to both ends of the aptamer sequence of vascular endothelial growth factor 165 (VEGF165). The specific binding of VEGF165 to aptamer causes structural changes of aptamer, which shortens the distance betwee
DNA-CuNCs at both ends, triggers self-assembly and aggregation to induce fluorescence, and achieves target detection. Based on the specific shearing, joining and polymerization of DNA by nucleases, DNA-protected metal nanoclusters can be used for the detection of nucleases.

Cell Detectionr
Adding aptamer, small molecule ligands or antibodies that can specifically recognize cells on the surface of metal nanoclusters or the nanomaterials composited with them can establish sensors for cell detection.

Application of Metal Nanoclusters in Tumor Treatment

Another important research direction of metal nanoclusters in the field of biomedicine is bioimaging. Compared with organic fluorescent dyes, metal nanoclusters have good dispersibility and stronger resistance to photobleaching. Compared with quantum dots, metal nanoclusters do not involve the leakage of toxic heavy metal ions such as Pb and Cd, and exhibit excellent biocompatibility. Compared with large-sized fluorescent nanoparticles, ultra-small metal nanoclusters exhibit an ideal renal clearance rate, which can effectively avoid accumulation in the body caused by long-term circulation, thereby reducing potential toxic side effects. Therefore, metal nanoclusters have great potential for in vivo applications, and they have been successfully applied to live cell imaging, live tumor imaging, and live real-time dynamic tracer imaging.

Application of Metal Nanoclusters in Tumor Treatment

As an excellent imaging contrast agent, metal nanoclusters can be used for imaging-guided tumor therapy through surface functionalization or composite with other nano-therapeutic agents. Imaging-guided tumor therapy is conducive to real-time monitoring of the efficacy of therapeutic agents in vivo And pharmacokinetics, realizing the timely evaluation of the treatment effect, and providing a personalized medical model for tumor treatment.

Radiation Therapy

Radiotherapy uses high-energy ionizing radiation to kill cancer cells, thereby slowing down or inhibiting tumor growth. Gold nanoclusters (AuNCs) have a high energy absorption coefficient, which helps X-rays to be enriched in tumor tissues located by AuNCs. Therefore, AuNCs can be used as high-efficiency radiation sensitizers for radiotherapy. According to research, AuNCs can produce reactive oxygen free radicals that damage the nucleus and mitochondrial DNA under X-ray irradiation, leading to irreversible cell apoptosis. The AuNCs protected by GSH were found to be enriched in the transplanted tumors of mice by enhancing the osmotic retention (EPR) effect, and the high content of GSH ligand on the surface can activate the glutathione transporter in the body, which helps cancer cells to Mass uptake of AuNCs.

Chemotherapy

Chemotherapy is currently one of the mainstream methods of clinical cancer treatment. The rise of targeted drug delivery based on nanomaterials in recent years provides a new opportunity for the development of chemotherapy. The rich surface functional groups and ultra-small size of metal nanoclusters make them very suitable as nanocarriers for small molecule drugs. Using chemical modification or electrostatic hydrophobic interaction, small-molecule drugs can be loaded on the surface of metal nanoclusters in large quantities, and then through active and passive tumor targeting, the purpose of drug delivery can be achieved. Another drug delivery strategy for metal nanoclusters is to assemble nanocomposite carriers with other nanomaterials. These nanomaterials usually have a large specific surface area or a large internal cavity to achieve high flux loading of drugs, such as GO, mesoporous silica nanoparticles, CaP nanoparticles, and so on. The internal cross-linked part of some amphoteric polymer nanoparticles can embed hydrophobic drugs, which facilitates the in vitro and in vivo administration of hydrophobic drugs. In the nanocomposite carrier, the imaging function of metal nanoclusters can be used for real-time monitoring of drug positioning and release.

Photodynamic Therapy
Photodynamic therapy (PDT) is a photochemotherapy that uses photosensitizers to absorb light to generate reactive oxygen free radicals under aerobic conditions, thereby triggering cell death and tissue damage. Traditional photosensitizers are mostly small organic molecules with hydrophobic structure, which are easy to agglomerate in aqueous solution, which greatly reduces the effect of PDT. Studies have shown that AuNCs themselves can generate active oxygen free radicals, which can be directly used as photosensitizers in PDT, and that AuNCs protected by GSH can generate active oxygen free radicals under the excitation of light with three different wavelengths (532, 650 and 808 nm).