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A curcumin-loaded polymeric micelle as a carrier of a microRNA-21 antisense-oligonucleotide for enhanced anti-tumor effects in a glioblastoma animal model†
Biomaterials Science ( IF 5.8 ) Pub Date : 2018-01-02 00:00:00 , DOI: 10.1039/c7bm01088e Xiaonan Tan 1, 2, 3, 4, 5 , Gyeungyun Kim 1, 2, 3, 4, 5 , Dahee Lee 1, 2, 3, 4, 5 , Jungju Oh 1, 2, 3, 4, 5 , Minkyung Kim 1, 2, 3, 4, 5 , Chunxian Piao 1, 2, 3, 4, 5 , Jaewon Lee 1, 2, 3, 4, 5 , Min Sang Lee 6, 7, 8, 9 , Ji Hoon Jeong 6, 7, 8, 9 , Minhyung Lee 1, 2, 3, 4, 5
Biomaterials Science ( IF 5.8 ) Pub Date : 2018-01-02 00:00:00 , DOI: 10.1039/c7bm01088e Xiaonan Tan 1, 2, 3, 4, 5 , Gyeungyun Kim 1, 2, 3, 4, 5 , Dahee Lee 1, 2, 3, 4, 5 , Jungju Oh 1, 2, 3, 4, 5 , Minkyung Kim 1, 2, 3, 4, 5 , Chunxian Piao 1, 2, 3, 4, 5 , Jaewon Lee 1, 2, 3, 4, 5 , Min Sang Lee 6, 7, 8, 9 , Ji Hoon Jeong 6, 7, 8, 9 , Minhyung Lee 1, 2, 3, 4, 5
Affiliation
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A glioblastoma is a common primary brain tumor that expresses microRNA-21 (miR-21), which inhibits the expression of pro-apoptotic genes such as phosphatase and tensin homologue (PTEN) and programmed cell death 4 (PDCD4). Therefore, an antisense-oligonucleotide against miR-21 (miR21ASO) could have therapeutic effects for glioblastomas. In this study, curcumin was loaded into deoxycholic acid-conjugated polyethylenimine (DP) micelles. The curcumin-loaded DP micelle (DP-Cur) was evaluated as a carrier for the combined delivery of curcumin and miR21ASO. Gel retardation and heparin competition assays showed that DP-Cur formed stable complexes with miR21ASO. The anti-tumor effects of the combined delivery of curcumin and miR21ASO were evaluated in C6 glioblastoma cells. In vitro transfection showed that DP-Cur had an miR21ASO delivery efficiency similar to that of polyethylenimine (25 kDa, PEI25k) and DP. In the C6 cells, the delivery of miR21ASO using DP-Cur effectively reduced the miR21 level. The miR21ASO/DP-Cur complex induced apoptosis more effectively than the single delivery of curcumin or miR21ASO. The therapeutic effect of the miR21ASO/DP-Cur complex was also evaluated in an intracranial glioblastoma animal model. The miR21ASO/DP-Cur complex reduced the tumor volume more effectively than single therapy of curcumin or miR21ASO. Immunohistochemistry showed that PDCD4 and PTEN were induced in the miR21ASO/DP and miR21ASO/DP-Cur complex groups. Therefore, DP-Cur is an efficient carrier of miR21ASO and the combined delivery of miR21ASO and curcumin may be useful in the development of combination therapy for glioblastoma.
中文翻译：
载有姜黄素的聚合物胶束作为microRNA-21反义寡核苷酸的载体，可在胶质母细胞瘤动物模型中增强抗肿瘤作用†
胶质母细胞瘤是表达microRNA-21（miR-21）的常见原发性脑肿瘤，它会抑制促凋亡基因（如磷酸酶和张力蛋白同源物（PTEN））和程序性细胞死亡4（PDCD4）的表达。因此，针对miR-21的反义寡核苷酸（miR21ASO）可能对胶质母细胞瘤具有治疗作用。在这项研究中，姜黄素被装入结合了脱氧胆酸的聚乙烯亚胺（DP）胶束中。姜黄素负载的DP胶束（DP-Cur）被评估为姜黄素和miR21ASO联合递送的载体。凝胶阻滞和肝素竞争试验表明，DP-Cur与miR21ASO形成稳定的复合物。在C6胶质母细胞瘤细胞中评估了姜黄素和miR21ASO联合递送的抗肿瘤作用。体外转染表明DP-Cur具有与聚乙烯亚胺（25 kDa，PEI25k）和DP相似的miR21ASO传递效率。在C6细胞中，使用DP-Cur递送miR21ASO可有效降低miR21水平。与姜黄素或miR21ASO的单次递送相比，miR21ASO / DP-Cur复合物能更有效地诱导凋亡。还在颅内成胶质细胞瘤动物模型中评估了miR21ASO / DP-Cur复合物的治疗效果。与姜黄素或miR21ASO的单一疗法相比，miR21ASO / DP-Cur复合物可更有效地减少肿瘤体积。免疫组织化学显示在miR21ASO / DP和miR21ASO / DP-Cur复合物组中诱导了PDCD4和PTEN。所以，
更新日期：2018-01-02
中文翻译：
载有姜黄素的聚合物胶束作为microRNA-21反义寡核苷酸的载体，可在胶质母细胞瘤动物模型中增强抗肿瘤作用†
胶质母细胞瘤是表达microRNA-21（miR-21）的常见原发性脑肿瘤，它会抑制促凋亡基因（如磷酸酶和张力蛋白同源物（PTEN））和程序性细胞死亡4（PDCD4）的表达。因此，针对miR-21的反义寡核苷酸（miR21ASO）可能对胶质母细胞瘤具有治疗作用。在这项研究中，姜黄素被装入结合了脱氧胆酸的聚乙烯亚胺（DP）胶束中。姜黄素负载的DP胶束（DP-Cur）被评估为姜黄素和miR21ASO联合递送的载体。凝胶阻滞和肝素竞争试验表明，DP-Cur与miR21ASO形成稳定的复合物。在C6胶质母细胞瘤细胞中评估了姜黄素和miR21ASO联合递送的抗肿瘤作用。体外转染表明DP-Cur具有与聚乙烯亚胺（25 kDa，PEI25k）和DP相似的miR21ASO传递效率。在C6细胞中，使用DP-Cur递送miR21ASO可有效降低miR21水平。与姜黄素或miR21ASO的单次递送相比，miR21ASO / DP-Cur复合物能更有效地诱导凋亡。还在颅内成胶质细胞瘤动物模型中评估了miR21ASO / DP-Cur复合物的治疗效果。与姜黄素或miR21ASO的单一疗法相比，miR21ASO / DP-Cur复合物可更有效地减少肿瘤体积。免疫组织化学显示在miR21ASO / DP和miR21ASO / DP-Cur复合物组中诱导了PDCD4和PTEN。所以，
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