Chondroitin Sulfate Thiol

Chondroitin sulphate (CS) is a sulphated glycosaminoglycan heteromer composed of alternating 1,4-linked N-acetyl-β-D-galactosamine (β-D-GalNAc) and 1,3-linked β-D-glucuronic acid (β-D-GlcA) disaccharide units. CS can be divided into several types, including CS-O, CS-A, CS-B, CS-C, CS-D and CS-E, according to the number and position of sulphate substitutions in acetyl GalNAc and GlcA. As the most abundant glycosaminoglycan in the human body and an important component of cartilage and the extracellular matrix, CS is present in large quantities in tissues such as skin, cartilage, tendon, heart valve and the central nervous system, and plays important physiological roles in the body, It plays important physiological roles in the body, such as participating in the formation of cartilage and bone, regulating growth factors such as fibroblast growth factor-2 and transforming growth factor-β, promoting wound healing, anti-inflammatory, anticoagulant, antioxidant, anti-tumor and enhancing immune response. Because of these physiological activities of CS, it is widely used in the clinic, including in combination with glucosamine to treat osteoarthritis. It can also be used to treat visual fatigue, neuralgia, joint pain and anti-inflammation. It is also because of the various physiological functions of CS, its excellent water solubility and negative charge, and the presence of carboxyl and hydroxyl groups in its structure, which are easy to modify, that CS can be used to construct a variety of biomaterials, such as nano-drug carriers for tumor diagnosis and treatment, and scaffold materials for tissue engineering.

Figure 1. Structure of the repeating units of oversulfated chondroitin sulfate.(Fonseca RJ, et al.; 2011)

Experiments have shown that drug carriers constructed using CS have suitable kinetic diameters, controllable surface charges, optimal encapsulation rates, non-toxicity and resistance. Due to its strong affinity with CD44, CS drug carriers designed using CD44 receptor-mediated endocytosis are a hot topic in tumor treatment research. CS can be made into CS hydrogels, CS nanoparticles and CS nanocapsules for drug delivery. CS hydrogel: Bone marrow mesenchymal stem cells (MSCs) and their secretory factors have anti-inflammatory and anti-angiogenic properties as well as the ability to promote wound healing. Researchers prepared CS-hyaluronic acid viscoelastic gels to deliver freeze-dried MSCs. Experiments have shown that hydrogels can promote the healing of mechanical and chemical corneal burns in rats, and can also reduce scars and new blood vessels after alkaline corneal burns. Other researchers have developed a thermosensitive hydrogel carrier of CS and hydroxypropyl methylcellulose, which uses electrostatic bonding to load platelet lysates, synergistically stimulates cell proliferation, and can effectively treat corneal injuries. The concentration of glutathione in tumor tissue is much higher than that in normal tissue. CS can cross-link with glutathione-sensitive disulfide bonds and specifically degrade in tumor cells after CD44-mediated internalization, reducing toxicity to normal tissues. In addition, some people have used this principle to develop a programmable drug delivery system targeting CD44, using CS hydrogel shell to wrap the core particles of chemotherapy drugs. Within 24 hours, only less than 10% of free drugs were detected at plasma glutathione concentrations, and about 20% of free drugs were detected at normal tissue glutathione concentrations. At tumor glutathione concentrations, drug molecules can be released up to 50% within the first 30 minutes, and then continuously released within 24 hours. In vivo experiments have shown that the drug delivery system has CD44-targeted delivery capabilities and significantly enhances the inhibition of drugs on tumors. CS nanoparticles: The researchers designed redox/enzyme-responsive chondroitin sulfate-deoxycholic acid (CSCD) self-assembled nanoparticles. Since hyaluronidase-1 can degrade CS, the nanoparticles have glutathione/hyaluronidase-1 dual-sensitive drug release characteristics. Compared with simple administration, CSCD nanoparticles loaded with docetaxel can reduce the volume and lung metastasis of melanoma. Gene therapy has been a research hotspot in recent years. The use of nanoparticles as carriers in therapeutic gene targeted delivery can achieve the purpose of avoiding genetic material degradation, directional delivery, and improving transfection rate. Scientists have also prepared CS and cationic gelatin hybrid nanoparticles loaded with gene fragments, proving that the addition of polyanionic CS effectively reduces the cytotoxicity of cationic polymers and ensures a stable cell uptake rate and pDNA transfection rate. In addition, some people use CS to modify polyamide amide dendrimers to make nanoparticles, which improves the uptake efficiency of tumor cells for miR-34a loaded in the particles through CD44-mediated endocytosis, enhances the effect of inducing cell cycle arrest and cell apoptosis, and shows good safety. Non-starch polysaccharide macromolecules cannot be digested by enzymes in the stomach and small intestine, but can be hydrolyzed by microorganisms in the colon, so they are very suitable for preparing colon-targeted drug delivery systems. CS nanocapsules: In recent years, integrated drug delivery and diagnostic imaging drug delivery systems have become a research focus in the medical field. On the surface of metabolically active cancer cells, lactoferrin (LF) was found to increase its binding to lactoferrin membrane internalization receptors (LRP1, LRP2) and transferrin receptors (TFR1, TFR2). Quantum dots (QD) are semiconductor nanoparticles with high fluorescence yield. Under the electron/energy transfer mechanism, when QD binds to lactoferrin in vitro, QD is in a fluorescence quenching state. After being taken up by cells, the fluorescence function is restored, and it can be used as a fluorescence imaging probe for cancer cells. The researchers used layer-by-layer electrostatic assembly technology to prepare CS nanocapsules with fluorescent labeling function, loaded with poorly soluble drugs celecoxib and magnolol to treat breast cancer. CS with anionic properties is the middle layer, which can not only encapsulate lipid drug-loaded particles, but also bind cationic LF-QD conjugates to the capsule surface, which can be tracked in vivo using confocal laser scanning microscopy. The team also tried to bind a layer of cationic gelatin to the surface of fluorescent CS nanocapsules. Cationic gelatin can be degraded by matrix metalloproteinases overexpressed by tumors, further enhancing the specificity of capsule binding to tumor cells. Experiments have shown that nanocapsules effectively improve the water solubility of drugs, dual targeting enhances the drug uptake rate of tumor cells, significantly inhibits tumor growth, and in vivo immunogenicity experiments have proved the good biocompatibility of nanocapsules. This stable, safe, efficient, and multifunctional drug delivery system has strong development potential and broad application prospects.

Alternate Names:
Chondroitin sulfuric acid
CSA
CS
Chondroitin polysulfate

References:
1. Fonseca RJ, et al.; Effects of oversulfated and fucosylated chondroitin sulfates on coagulation. Challenges for the study of anticoagulant polysaccharides. Thromb Haemost. 2010, 103(5):994-1004.

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