Abbas Mohajeri
1,2, Sarvin Sanaei
2, Farhad Kiafar
1, Amir Fattahi
3, Majid Khalili
4, Nosratollah Zarghami
2,3,5*1 Department of Biotechnology, Zahravi Pharmaceutical Company, Tabriz, Iran.
2 Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
3 Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
4 Department of Basic Science, Maragheh University of Medical Sciences, Maragheh, Iran.
5 Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences,Tabriz, Iran.
*Corresponding Author: Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences,Tabriz, Iran. Email zarghami@tbzmed.ac.ir
Abstract
Angiogenesis plays an essential
role in rapid growing and metastasis of the tumors. Inhibition of angiogenesis
is a putative strategy for cancer therapy. Endostatin (Es) is an attractive
anti-angiogenesis protein with some clinical application challenges including;
short half-life, instability in serum and requirement to high dosage.
Therefore, production of recombinant endostatin (rEs) is necessary in large
scale. The production of rEs is difficult because of its structural properties
and is high-cost. Therefore, this review focused on the different expression
systems that involved in rEs production including; mammalian, baculovirus,
yeast, and Escherichia coli (E. coli) expression systems. The
evaluating of the results of different expression systems declared that none of
the mentioned systems can be considered to be generally superior to the other.
Meanwhile with considering the advantages and disadvantage of E. coli
expression system compared with other systems beside the molecular properties
of Es, E. coli expression system can be a preferred expression system
for expressing of the Es in large scale. Also, the molecular bioengineering and
sustained release formulations that lead to improving of its stability and
bioactivity will be discussed. Point mutation (P125A) of Es, addition of RGD
moiety or an additional zinc biding site to N-terminal of Es , fusing of Es to
anti-HER2 IgG or heavy-chain of IgG, and finally loading of the endostar by
PLGA and PEG- PLGA nanoparticles and gold nano-shell particles are the
effective bioengineering methods to overcome to clinical changes of endostatin.