In vitro evaluation of anti-angiogenesis property of anti-VEGFR۲ nanobody-conjugated H۴۰-PEG carrier loaded with methotrexate

  • سال انتشار: 1401
  • محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 25، شماره: 12
  • کد COI اختصاصی: JR_IJBMS-25-12_009
  • زبان مقاله: انگلیسی
  • تعداد مشاهده: 256
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نویسندگان

Seyed Masih Adyani

Pharmaceutical Biomaterials Department, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran

Hamid Rashidzadeh

Pharmaceutical Biomaterials Department, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran

Mahdi Behdani

Department of Molecular Medicine, Pasture Institute of Iran, Tehran, Iran

Seyed Jamal Tabatabaei Rezaei

Department of Chemistry, University of Zanjan, Zanjan, Iran

Ali Ramazani

Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran

چکیده

Objective(s): In this study, Boltorn® H۴۰-PEG-MTX-anti-VEGFR۲ nanobody was fabricated in which nanobody was selected for blocking the receptor, H۴۰ as a nanocarrier for delivery of methotrexate (MTX) to the tumor cells, and polyethylene glycol (PEG) moieties for improving the blood circulation time and safety. Materials and Methods: The synthesis process of the nanosystem has been characterized by different analytical methods. Results: The prepared nanoplatform exhibited high drug loading capacity, excellent colloidal stability, and an average particle size of around ۱۰۵ nm. MTX was successfully conjugated through ester bonds and its release profile clearly showed that the ester bond is in favor of releasing the drug in acidic pH (۵.۵). The cytotoxicity of the developed nanoplatform exhibited great anti-cancer activity against MCF۷ and KDR۲۹۳ (cells with overexpressed anti-VEGFR۲ NB receptors) cell lines while no deleterious toxicity was observed for nanocarrier against HEK۲۹۳ normal cells.  Furthermore, both hemolysis and LD۵۰ assay results confirmed the hemocompatibility and biocompatibility of the developed nanoplatform. Conclusion: The most striking result to derive from the data is that the designed nanoplatform could potentially inhibit cell migration and invasion and the anti-angiogenesis properties of the developed nanoplatform may serve as a promising nanosystem to suppress the formation of blood vessels around tumor cells and consequently inhibit tumor progression.

کلیدواژه ها

Angiogenesis inhibitors, Methotrexate, Polymer, Single-domain antibodies, Vascular endothelial - Growth factor receptor-۲

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