How The Liver-Targeted Nano-Drug Delivery System Is Realized

Physiological characteristics of the liver The liver is an important organ involved in the processes of digestion, excretion, detoxification and immunity. Liver diseases are common clinical diseases, such as viral hepatitis, cirrhosis and liver cancer, which are extremely harmful to human health. The liver-targeted drug delivery system is an important way to explore an effective treatment method for liver disease, as it enriches the drug at the site of the liver lesion to exert the curative effect, reducing the amount of drug and the number of drug administration. Liver cells are divided into hepatic parenchymal cells, Kupffer cells and endothelial cells, of which parenchymal cells are the main cells that make up the liver, accounting for 80% of the volume and number of the liver. Most metabolic activities of the liver are concentrated in parenchymal cells, which contain hundreds of enzymes. Most liver-related diseases such as liver cancer, hepatitis, and cirrhosis occur in parenchymal cells. The liver is also rich in phagocytic cells-Kupffer cells, which can phagocytose and clear foreign bodies in the blood, and are a major component of the body’s defense system. Therefore, different types of liver targeting preparations can be designed for different types of cells in livers. Passive targeting After intravenous injection of the nanometer drug delivery system, it can be swallowed by Kupffer cells in the liver, causing the drug to accumulate in the liver, and reduce adverse reactions to other organs, which is passive targeting. Active targeting 1). Receptor-mediated active targeting Asialoglycoprotein receptor (ASGPR) and transferrin receptor are present on hepatic parenchymal cell membranes. There are mannose receptors, low-density lipoprotein receptors and clearance receptors on the non-parenchymal cell membrane. Active targeting of drugs or carriers modified by different receptors can be achieved through receptor ligand-specific interactions. Radioligand binding experiments and separation of hepatocytes and cell membranes have shown that mammalian hepatocytes have a receptor on the cell membrane of the sinusoidal side, called asialoglycoprotein receptor (ASGPR), which specifically recognizes the end A glycoprotein containing galactose or acetylgalactose. Ligands for modifying drugs or carriers based on ASGPR include β-D-galactose (β-D-Gal), galactosylceramide, trigalactosylcholesterol, galactosylphosphatidylethanolamine, asialo fetuin (AF ) and synthetic glycoproteins (so-called neoglycoproteins). 2). Antibody-mediated active targeting The nanoparticles are cross-linked with anti-human liver cancer monoclonal antibodies (McAbs) to form drug-nanoparticle-mab antibody complexes, that is, immune-targeting nanoparticles, which can enhance the liver-targeting properties of the nanoparticles. Doxorubicin poly-n-butyl cyanoacrylate nanoparticles are combined with highly specific monoclonal antibodies against human liver cancer acid iso-ferritin to obtain liver cancer-specific immune nanoparticles. Animal in vivo tests have shown that the drug half-life is significantly prolonged. In vitro cytotoxicity tests and in vivo tumor suppression tests in nude mice have shown high efficiency and strong targeting. Most of the drugs are concentrated in liver tumors, which greatly reduces the toxicity to other organs. 3). Magnetic nanoparticles Loading liver-targeted drugs into magnetic nanoparticles and injecting a magnetic field in the liver tumor area after hepatic artery injection can significantly increase the drug concentration of tumor tissue in the magnetic area. Nanocarriers have good liver targeting, biocompatibility, sustained release, and modifiability, which can significantly increase the concentration of the drug in the liver, enhance the efficacy, and reduce the toxic and side effects of the drug. However, nanocarriers have problems with drug loading and encapsulation efficiency and the stability and integrity of biological macromolecules, as well as problems with gene transfection efficiency, prolonged circulation in the body, and increased sustained release. With the continuous development and utilization of nano-materials and processes, nano-technology continues to mature, and nanoparticles will play an important role in liver-targeted applications.