N-acetylglucosamine is a compound in which one hydroxyl group of glucose is replaced by an amino group. It is the most abundant and widely distributed class of organic compounds in organisms and is involved in many important physiological functions. Studies have shown that sugar is not only a structural component of cells, but also a major source of energy and storage material. Among them, monosaccharides such as glucose are the main source of energy in the metabolic process and participate in the biosynthesis process. Certain sugar derivatives are not only important components of coenzymes, but also can constitute the skeleton of genetic material. In addition, sugar plays an important role in physiological processes such as intercellular signal transduction, antibody recognition, hormone system, and musculoskeletal system. Therefore, N-acetylglucosamine, as an important carbohydrate compound in the body, plays an important role in physiological processes. For example, N-acetylglucosamine is the synthetic precursor of the disaccharide unit of glycosaminoglycans, is the main structure of osteoarticular cartilage, and plays an important role in repairing and maintaining the function of cartilage and joint tissues.
Figure 1. N-acetyl-D-glucosamine modified nanolipid carriers for targeted delivery of anticancer drugs. (Rahul Kumar, et al.; 2022)
N-acetylglucosamine (a derivative of glucose in which a hydroxyl group is replaced by an amino group, systematically named 2-acetyl-2-deoxy-D-glucose, is widely present in nature. Its molecular formula is C6H13NO5, usually white or slightly yellow powder, slightly sweet, melting point 221°C. The solubility in water is 25%, and the 1% aqueous solution is colorless and transparent. N-acetylglucosamine exists in all organisms. In the human body, it is the disaccharide unit precursor of glucosamine polysaccharides such as hyaluronic acid, chondroitin sulfate and keratan sulfate. N-acetylglucosamine specifically acts on articular cartilage and plays an important role in maintaining the health of cartilage and normal joint function. N-acetylglucosamine can increase the content of hyaluronic acid in the skin; in addition, N-acetylglucosamine is also a precursor for the synthesis of acetylneuraminic acid. Interesting, N-acetylglucosamine is also the monomer unit of chitin, forming a linear polymer with glycosidic bonds. Chitin is the second largest biomass resource in nature after cellulose. N-acetylglucosamine can not only form homopolysaccharides such as chitin, but also some heteropolysaccharides such as peptidoglycan, hyaluronic acid and chondroitin. The peptidoglycan skeleton is a polysaccharide chain formed by alternating N-acetylglucosamine and acetylmuramic acid residues, which is the basic component of the cell wall of microorganisms.
GlcNAc is gaining attention as a drug carrier in modern drug delivery systems. N-acetylglucosamine is widely found in glycosaminoglycans and glycoproteins and plays an important role in the body. Its advantages as a pharmaceutical carrier are mainly reflected in the following aspects. First, N-acetylglucosamine has excellent biocompatibility, which makes it highly compatible with polysaccharides and glycoproteins in living organisms, thereby reducing immune responses and toxicity. This biocompatibility is crucial to ensure the safety and efficacy of drug delivery systems. Secondly, N-acetylglucosamine can combine with specific cell surface receptors to achieve targeted delivery to target cells. This kind of targeting can not only improve the therapeutic effect of the drug, but also reduce the impact on non-target cells, thus reducing side effects. Third, N-acetylglucosamine can improve the stability and bioavailability of drugs as a drug carrier. GlcNAc carriers can protect the contained drugs from degradation by binding to drug molecules, which will enhance their stability in the body and thereby increase the effective concentration and action time of the drug. Furthermore, N-acetylglucosamine has good potential for functionalization. Through chemical modification, additional functions can be given to it, such as enhancing the control ability of drug release and improving the solubility and penetration ability of drugs. This ability to functionalize enables N-acetylglucosamine to meet the needs of different drug delivery systems, thereby improving therapeutic efficacy and patient compliance. Taken together, N-acetylglucosamine has great potential as a drug carrier and shows broad application prospects in cancer treatment, gene therapy and other drug delivery systems. Its excellent biocompatibility, targeting, stability improvement ability and functionalization potential make it a material of great concern in the field of drug delivery.
Alternate Names:
N-acetylglucosamine
GlcNAc
Acetyl-D-glucosamine
2-Acetamido-2-deoxy-D-glucose
NAG
References:
1. Rahul Kumar, et al.; N-acetyl-d-glucosamine decorated nano-lipid-based carriers as theranostics module for targeted anti-cancer drug delivery. Materials Chemistry and Physics. 2022, Volume 282, 125956.
2. Pooja D, et al.; N-acetyl-d-glucosamine-conjugated PAMAM dendrimers as dual receptor-targeting nanocarriers for anticancer drug delivery. Eur J Pharm Biopharm. 2020, 154:377-386.
N-acetyl-d-glucosamine-conjugated PAMAM dendrimers as dual receptor-targeting nanocarriers for anticancer drug delivery
Eur J Pharm Biopharm.
Authors: Pooja D, Srinivasa Reddy T, Kulhari H, Kadari A, Adams DJ, Bansal V, Sistla R.
Abstract
N-acetyl-d-glucosamine-labelled dendrimers (NAG-Dend) were synthesized for the targeted delivery of camptothecin (CPT) to A549 human lung adenocarcinoma cells, which overexpress glucose transporters and lectin receptors. CPT loaded, NAG-Dend (NAG-Dend-CPT) exhibited more rapid and higher cellular uptake than the unlabelled dendrimer formulation (Dend-CPT), leading to enhanced cytotoxicity. Compared with native CPT, NAG-Dend-CPT was 4.5 times more toxic to A549 cells. The anticancer activity of the different CPT formulations was dose and time dependent. NAG-Dend-CPT also increased reactive oxygen species generation, induced higher apoptosis and showed greater inhibition of A549 cell migration than Dend-CPT. The selective accumulation of NAG-Dend in the lungs of tumour-bearing mice confirmed that the NAG-based dendrimer system can target lung metastasis tumours in a biological system. Overall, our results show that NAG-conjugated dendrimers could be a promising nanocarrier system for the delivery of anticancer drugs, including CPT, to human lung cancer cells.
Folate/N-acetyl glucosamine conjugated mesoporous silica nanoparticles for targeting breast cancer cells: A comparative study
Colloids Surf B Biointerfaces
Authors: Kumar P, Tambe P, Paknikar KM, Gajbhiye V.
Abstract
Folate receptors (FR) have been well recognized as a marker to target nano-sized carriers for cancer diagnosis and therapy. In contrast, influx transport systems (e.g. GLUT transporters) that transport essential amino acids and nutrients to cancer cells have not been exploited much for targeted delivery. In this study, folic acid- or n-acetyl glucosamine- functionalized mesoporous silica nanoparticles loaded with doxorubicin (DOX-FA-MSNPs or DOX-NAG-MSNPs) were prepared, characterized and compared for targeting along with cytotoxicity towards MCF-7 and MDA-MB-231 human breast cancer cells. Cellular uptake of FITC tagged FA-MSNPs and NAG-MSNPs were evaluated by confocal microscopy and flow cytometry in above-mentioned cancer cell lines. The result suggested higher cellular uptake of NAG-MSNPs than FA-MSNPs for both the cell lines. Cytotoxicity of free DOX, DOX-MSNPs, DOX-FA-MSNPs and DOX-NAG-MSNPs were evaluated on both the breast cancer cell lines. Cytotoxicity results showed that DOX-loaded NAG-MSNPs exerted significant higher cytotoxicity effect on both the cell lines than DOX-FA-MSNPs. Moreover, both the targeted formulations were more effective than free DOX. Our results suggested that GLUT transporters can be effectively utilized for nanoparticles internalization in breast cancer cells.
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