این سایت در حال حاضر پشتیبانی نمی شود و امکان دارد داده های نشریات بروز نباشند
Avicenna Journal of Medical Biotechnology، جلد ۱۳، شماره ۲، صفحات ۵۸-۶۴
عنوان فارسی
چکیده فارسی مقاله
کلیدواژه‌های فارسی مقاله
عنوان انگلیسی Designing and Development of a Tandem Bivalent Nanobody against VEGF165
چکیده انگلیسی مقاله Background: Inhibition of angiogenesis using monoclonal antibodies is an effective strategy in cancer therapy. However, they could not penetrate sufficiently into solid tumors. Antibody fragments have solved this issue. However, they suffer from short in vivo half-life. In the current study, a tandem bivalent strategy was used to enhance the pharmacokinetic parameters of an anti-VEGF165 nanobody. Methods: Homology modeling and MD simulation were used to check the stability of protein. The cDNA was cloned into pHEN6C vector and the expression was investigated in WK6 Escherichia coli (E. coli) cells by SDS-PAGE and western blot. After purification, the size distribution of tandem bivalent nanobody was investigated by dynamic light scattering. Moreover, in vitro antiproliferative activity and pharmacokinetic study were studied in HUVECs and Balb/c mice, respectively. Results: RMSD analysis revealed the tandem bivalent nanobody had good structural stability after 50 ns of simulation. A hinge region of llama IgG2 was used to fuse the domains. The expression was induced by 1 mM IPTG at 25°C for overnight. A 30 kDa band in 12% polyacrylamide gel and nitrocellulose paper has confirmed the expression. The protein was successfully purified using metal affinity chromatography. MTT assay revealed there is no significant difference between the antiproliferative activity of tandem bivalent nanobody and the native protein. The hydrodynamic radius and terminal half-life of tandem bivalent nanobody increased approximately 2-fold by multivalency compared to the native protein. Conclusion: Our data revealed that the physicochemical as well as in vivo pharmacokinetic parameters of tandem bivalent nanobody was significantly improved.
کلیدواژه‌های انگلیسی مقاله Cancer, Pharmacokinetics, Single domain antibody, Vascular endothelial growth factor
نویسندگان مقاله | Farnaz Khodabakhsh
Department of Genetics and Advanced Medical Technology, Medical Biotechnology Research Center, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran


| Morteza Salimian
Department of Medical Laboratory, Kashan University of Medical Sciences, Kashan,


| Pardis Ziaee
Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran


| Fatemeh Kazemi-Lomedasht
Venom and Biotherapeutics Molecules Laboratory, Department of Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran


| Mahdi Behdani


| Reza Ahangari Cohan


نشانی اینترنتی https://www.ajmb.org/En/Article.aspx?id=40451
فایل مقاله فایلی برای مقاله ذخیره نشده است
کد مقاله (doi)
زبان مقاله منتشر شده en
موضوعات مقاله منتشر شده
نوع مقاله منتشر شده
برگشت به: صفحه اول پایگاه   |   نسخه مرتبط   |   نشریه مرتبط   |   فهرست نشریات