Polymers for Intracellular Delivery of Proteins

MIRA Institute of Biomedical Technology and Technical Medicine, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands Email J.F.J.Engbersen utwente.nl 

The rapid development of genomics and proteomics during the last two decades has led to the discovery of several hundreds of proteins with powerful and selective activity in important physiological processes. Together with increasing technology development for production of these proteins on a commercial viable scale, protein therapeutics have become of an increasing interest as potential leads for the pharmaceutical market.  

The most frequently marketed hiopharmaceuticals include monoclonal antihody-hased products for cancer treatment and autoimmune diseases, therapeutic vaccines, insulin for diabetes treatment, human growth hormone for supplementation in hormone deficiency, and interferon-a for treatment of hepatitis B and/or C. Some protein agents such as vaccines, hormones, growth factors and enzymes have the opportunity to be used 

Many of these proteins should exert their pharmaceutical action inside the cytoplasm or in individual organelles inside the cell, as for instance toxins against cancer cells like ricin and gelonin, nucleases and antibodies like ot-tubulin. ° The average eukaryotic cell contains thousands of proteins participating in its normal cellular functions, of which many can be considered as a potential lead for the development of new therapeutics/  

Intracellular protein delivery is considered to be the most direct, fastest and safest approach for curing gene-deficiency diseases or disorders affecting primarily cellular processes, such as cystic fibrosis, coagulation disorders, otl-antitrypsin deficiency, immunoglobulin deficiencies, endocrine disorders and lysosomal storage diseases, where the expression of required proteins in the host cells is limited due to the defects in the required cellular (endogenous transcriptional) machinery/  

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To date, a variety of methods have been developed for the efficient delivery of QDs into cells [204, 205]. These include nonspecific endocytosis [206-209] or receptor-mediated endocytosis that involves QDs decorated with transfection reagents (peptides [210-215], proteins [65, 216-219], cationic liposomes [204], dendrimers [204], polymers [220,221] or small molecules [222,223]) that were used for the intracellular delivery of QDs. Physical techniques such as, electroporation [204, 224] or microinjection [204, 225, 226] have also been employed to deliver QDs into cells. 

Stayton PS, Hoffman AS, Murthy N, Lackey C, Cheung C, Tan P, Klumb LA, Chilkoti A, Wilbur ES, Press OW (2000) Molecular engineering of proteins and polymers for targeting and intracellular delivery of thertqteutics. J Controlled Release 65 203-220... 

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