Strategies for the enhancement of anti-cancer effect of phosphodiesterase type 5 inhibitors using drug binding fusion proteins

IF 2.5 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Hongbin Kim, Chang Yeop Keum, Su Yeon Lim, Kwang Suk Lim
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Abstract

Drug repurposing is a rapidly growing for the development of new therapeutic agents. Among them, phosphodiesterase-5 (PDE5) inhibitors, which show excellent effects as a treatment for erectile dysfunction, have been continuously reported for their potential as anti-cancer agents. It is necessary to apply targeted delivery systems to enhance the efficacy of the PDE5 inhibitors (PDE5i) as anti-cancer drugs. In this study, PDE5 inhibitor-binding domain (PBD) was developed to incorporate PDE5i into antibody using biological affinity binding without any chemical modifications. The PBD spontaneously bound with PDE5i, resulting in the formation of PBD/PDE5i complex. We also constructed a recombinant fusion protein composed of an anti-HER2 scFv and PBD (HER2 scFv-PBD) to deliver the PDE5i for the treatment of HER2 positive cancer cells. HER2 scFv-PBD could deliver the PDE5i into HER2-positive cancer cells and enhanced anti-cancer effect of the PDE5i. We have demonstrated the potential of tumor-directed PDE5 inhibition as a novel form of targeted therapy using drug binding fusion proteins.

Abstract Image

利用药物结合融合蛋白增强 5 型磷酸二酯酶抑制剂抗癌效果的策略
在开发新的治疗药物方面,药物再利用正在迅速发展。其中,磷酸二酯酶-5(PDE5)抑制剂在治疗勃起功能障碍方面效果显著,但其作为抗癌药物的潜力也不断被报道。有必要应用靶向给药系统来提高 PDE5 抑制剂(PDE5i)作为抗癌药物的疗效。本研究开发了 PDE5 抑制剂结合域(PBD),利用生物亲和力将 PDE5i 结合到抗体中,无需任何化学修饰。PBD 自发与 PDE5i 结合,形成 PBD/PDE5i 复合物。我们还构建了一种由抗 HER2 scFv 和 PBD 组成的重组融合蛋白(HER2 scFv-PBD)来递送 PDE5i,用于治疗 HER2 阳性的癌细胞。HER2 scFv-PBD 可将 PDE5i 送入 HER2 阳性癌细胞,增强 PDE5i 的抗癌效果。我们利用药物结合融合蛋白证明了肿瘤定向 PDE5 抑制作为一种新型靶向疗法的潜力。
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来源期刊
Biotechnology and Bioprocess Engineering
Biotechnology and Bioprocess Engineering 工程技术-生物工程与应用微生物
CiteScore
5.00
自引率
12.50%
发文量
79
审稿时长
3 months
期刊介绍: Biotechnology and Bioprocess Engineering is an international bimonthly journal published by the Korean Society for Biotechnology and Bioengineering. BBE is devoted to the advancement in science and technology in the wide area of biotechnology, bioengineering, and (bio)medical engineering. This includes but is not limited to applied molecular and cell biology, engineered biocatalysis and biotransformation, metabolic engineering and systems biology, bioseparation and bioprocess engineering, cell culture technology, environmental and food biotechnology, pharmaceutics and biopharmaceutics, biomaterials engineering, nanobiotechnology, and biosensor and bioelectronics.
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