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The Utilization of Poly(2‐ethyl‐2‐oxazoline)‐b‐Poly(ε‐caprolactone) Ellipsoidal Particles for Intracellular BIKDDA Delivery to Prostate Cancer
Macromolecular Bioscience ( IF 4.4 ) Pub Date : 2020-11-16 , DOI: 10.1002/mabi.202000287
Polen Kocak 1 , Umut Can Oz 2 , Zeynep Busra Bolat 1, 3 , Umut Ugur Ozkose 4, 5, 6 , Sevgi Gulyuz 4, 5 , Mehmet Atilla Tasdelen 7 , Ozgur Yilmaz 4 , Asuman Bozkir 2 , Fikrettin Sahin 1 , Dilek Telci 1
Affiliation  

Prostate cancer is the most common cancer, which is about 15–20% among male cancers worldwide. As most common strategies such as radiotherapy, chemotherapy, or surgery alone can be unsuccessful in the treatment of prostate cancer, this study aims to develop a new approach to deliver newly generated proapoptotic gene, BIKDDA, to androgen independent prostate cancer cells, 22RV1, using new generation nanocarriers called ellipsoids. As far as it is known, this is the first study that assesses the ability of proapoptotic gene BIKDDA to induce apoptosis in prostate cancer cell. BIKDDA encapsulating PEtOx‐b‐PCL‐based ellipsoids are fabricated by solvent‐switch method, and their morphology, size, and BIKDDA content are characterized. Gene delivery efficiency of BIKDDA loaded PEtOx‐b‐PCL ellipsoids is demonstrated by analysis of BIK mRNA expression with real‐time PCR. The apoptotic effect of PEtOx‐b‐PCL ellipsoids loaded with BIKDDA (EPs‐BIKDDA) on 22RV1 is shown by Annexin V staining. The obtained results demonstrate that the treatment of 22RV1 cells with EPs‐BIKDDA can significantly increase BIK mRNA levels by 4.5‐fold leading to cell death. This study not only represents BIKDDA as a potential therapeutic strategy in prostate cancer but also the capacity of ellipsoids as promising in vivo gene delivery vehicles.

中文翻译:

聚(2-乙基-2-恶唑啉)-b-聚(ε-己内酯)椭圆体颗粒在细胞内 BIKDDA 递送至前列腺癌中的应用

前列腺癌是最常见的癌症,约占全球男性癌症的 15-20%。由于放疗、化疗或单独手术等最常见的策略在前列腺癌的治疗中可能不成功,因此本研究旨在开发一种新方法,将新生成的促凋亡基因 BIKDDA 递送至雄激素非依赖性前列腺癌细胞 22RV1,使用称为椭圆体的新一代纳米载体。据了解,这是第一项评估促凋亡基因BIKDDA诱导前列腺癌细胞凋亡能力的研究。BIKDDA 封装的 PEtOx - b -PCL 基椭球是通过溶剂转换法制备的,并表征了它们的形态、尺寸和 BIKDDA 含量。BIKDDA 负载的 PEtOx- b 的基因传递效率‐PCL 椭球体通过实时 PCR 分析 BIK mRNA 表达来证明。载有 BIKDDA (EPs-BIKDDA) 的 PEtOx- b- PCL 椭球体对 22RV1 的凋亡作用通过膜联蛋白 V 染色显示。获得的结果表明,用 EPs-BIKDDA 处理 22RV1 细胞可以使 BIK mRNA 水平显着增加 4.5 倍,导致细胞死亡。这项研究不仅表明 BIKDDA 作为前列腺癌的潜在治疗策略,而且还表明椭球体作为有希望的体内基因传递载体的能力。
更新日期:2020-11-16
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