Polyethylene Glycol (PEG) Modification in Antitumor Drugs

PEGylation modification is the chemical coupling of activated polyethylene glycol (PEG) to proteins, peptides, small organic drugs and liposomes. As an excipient of traditional pharmaceutical preparations, PEG has been widely used in antitumor drug delivery systems due to its unique physical and biological properties.

PEG-based anti-tumor drug technology can prolong the half-life and enhance the stability of the drug, and reduce the immunogenicity and antigenicity. By changing the drug's molecular structure, the pharmacokinetic and pharmacodynamic properties are improved, and the blood drug concentration at the site of action is increased. At the same time, compared with unmodified drugs, PEGylated drugs show better tolerability, thus increasing the scope of clinical application and efficacy of injected drugs. PEGylated anti-tumor drugs have become increasingly studied in the field of anti-tumor drug research.

Polyethylene Glycol (PEG) Modification in Antitumor Drugs

PEG modification and small molecule antitumor drugs

For many years, the drawbacks of many small molecule anti-tumor drugs, such as poor water solubility, low bioavailability, short half-life in vivo, irrational tissue distribution, and strong toxicity and side effects, have been restricting their development.

PEG is often used as a carrier to load small molecule drugs, such as paclitaxel, camptothecin, doxorubicin, etc., to improve their pharmacokinetic and pharmacodynamic properties. After being modified by PEG, the water solubility, half-life of circulation in vivo, and adverse reactions of these drugs can be greatly improved. In addition, the formed macromolecular complex can significantly enhance permeability and retention effect (EPR) and has a passive targeting effect on tumor tissues.

PEG modification and protein antitumor drugs

Traditional protein and peptide drugs will degrade after encountering acid and digestive enzymes in the digestive tract and become amino acids, thus losing their efficacy. At present, most biological protein drugs are injections and must be stored in cold storage, which is very inconvenient for patient use.

PEG is a hydrophilic, uncharged macromolecule. When PEG is covalently bound to non-essential groups of protein drugs, it can act as a barrier to block the antigenic determinants on the surface of the protein molecule, avoid the production of antibodies, or prevent the binding of antigens and antibodies to inhibit the immune response. At the same time, the shielding effect of PEG can prevent the protein from being degraded by enzymes, thereby increasing the stability of the protein. On the other hand, the modified protein increases the molecular weight, is not easily metabolized by the kidneys, and prolongs the half-life of the drug in the body, thus reducing the number of medications.

PEG modification and enzyme antitumor drugs

Enzyme drugs treat tumors by reducing the amount of essential amino acids in tumor cells.

Long-term consumption of certain amino acids may cause the death of cancer cells. This requires enzyme drugs to have a longer blood circulation time in the body. However, under normal circumstances, native enzymes are prone to protein degradation, which is then quickly eliminated in the kidneys and easily produces a strong host immune response. Therefore, they are usually in the body for a very short time. The immunogenicity of enzyme drugs can greatly interfere with their use, because after multiple administrations, it easily induces the production of an immune response from the body, resulting in less effective blood drug concentrations in subsequent administrations.

One of the solutions to the above problems is to use enzyme isomers from different origins. However, this method cannot completely solve the problem, because the isomer itself still has a certain degree of immunogenicity. A more effective solution is the PEG modification. PEGylation can eliminate the immunogenicity of the protease, increase the circulation time of the drug in the body, make the drug not easily cleared by the kidney, and avoid degradation.

Creative Proteomics can provide customers with pegylated protein drug analysis services.


  • Mishra, Prajna, Bismita Nayak, and R. K. Dey. "PEGylation in anti-cancer therapy: An overview." asian journal of pharmaceutical sciences 11.3 (2016): 337-348.

*For Research Use Only. Not for use in the treatment or diagnosis of disease.

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