Protein PEGylation for cancer therapy: bench to bedside

Abstract

PEGylation is a biochemical modification process of bioactive molecules with polyethylene glycol (PEG), which lends several desirable properties to proteins/peptides, antibodies, and vesicles considered to be used for therapy or genetic modification of cells. However, PEGylation of proteins is a complex process and can be carried out using more than one strategy that depends on the nature of the protein and the desired application. Proteins of interest are covalently conjugated or non-covalently complexed with inert PEG strings. Purification of PEGylated protein is another critical step, which is mainly carried out based on electrostatic interactions or molecular sizes using chromatography. Several PEGylated drugs are being used for diseases like anemia, kidney disease, multiple sclerosis, hemophilia and cancers. With the advancement and increased specificity of the PEGylation process, the world of drug therapy, and specifically cancer therapy could benefit by utilizing this technique to create more stable and non-immunogenic therapies. In this article we describe the structure and functions of PEGylation and how this chemistry helps in drug discovery. Moreover, special emphasis has been given to CCN-family proteins that can be targeted or used as therapy to prevent or block cancer progression through PEGylation technology.

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Availability of data and material

All data generated or analyzed during this study are included in this published article.

Abbreviations

PEG:

Polyethylene glycol

NP:

Nanoparticle

MW:

Molecular weight

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Acknowledgements

We thank the members of Kansas City VA Research Office and Midwest Biomedical Research Foundation Administrative and clerical supports.

Funding

The work is supported by Merit review grant from Department of Veterans Affairs (Sushanta K. Banerjee, 5I01BX001989–04 and Snigdha Banerjee, I01BX001002–05), KUMC Lied Basic Science Grant Program (SKB), and Grace Hortense Greenley Trust, directed by The Research Foundation in memory of Eva Lee Caldwell (SKB). This work is partially supported by NIH grant P20 GM109024 from the National Institute of General Medical Science (NIGMS) (MQ), NSF under Grant No.  092354 (MQ), NIH Grant Number 2P20 RR015566 from the National Center for Research Resources (MQ), NIH grant 1R01 GM 114080 (NIGMS) and NSF Grant No. IIA-1355466 from North Dakota Established Program to Stimulate Comperative Research (EPSCoR) through the Center for Sustanable Materials Science (MQ).

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Contributions

Conception and design: S. K. Banerjee, S. Banerjee, M. Quadir, and V. Gupta, A. Ghosh; Writing and review of the manuscript: V. Gupta, M. Quadir, S. Bhavanasi, G. Ghosh, T. Siahaan, and S.K. Banerjee; Administrative, technical or material support: M. Quadir and S. K. Banerjee, and Study supervision: S. K. Banerjee.

Corresponding authors

Correspondence to Mohiuddin Quadir or Snigdha Banerjee or Sushanta K. Banerjee.

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All the authors of this manuscript have agreed to publish this article.

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No potential conflicts of interest were disclosed.

Additional information

Sneha Bhavanasi, Kevin Singh, Gaurav Ghosh and Kritin Vasamreddy Summer students

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Gupta, V., Bhavanasi, S., Quadir, M. et al. Protein PEGylation for cancer therapy: bench to bedside. J. Cell Commun. Signal. 13, 319–330 (2019). https://doi.org/10.1007/s12079-018-0492-0

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Keywords

  • PEGylation
  • Cancer
  • Polyethylene glycol
  • Nanoparticles
  • Immunogenicity