当前位置：
X-MOL 学术
›
Mol. Pharmaceutics
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Treatment of Melanoma by Nano-conjugate-Delivered Wee1 siRNA
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2021-08-10 , DOI: 10.1021/acs.molpharmaceut.1c00316 Xueyan Zhang 1 , Anqi Cai 1 , Yan Gao 1 , Yuanfa Zhang 1 , Xingmei Duan 2 , Ke Men 1
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2021-08-10 , DOI: 10.1021/acs.molpharmaceut.1c00316 Xueyan Zhang 1 , Anqi Cai 1 , Yan Gao 1 , Yuanfa Zhang 1 , Xingmei Duan 2 , Ke Men 1
Affiliation
|
Small interfering RNA (siRNA)-based drugs have shown tremendous potential to date in cancer gene therapy. Despite the considerable efforts in siRNA design and manufacturing, unsatisfactory delivery systems persist as a limitation for the application of siRNA-based drugs. In this work, the cholesterol, cell-penetrating peptide conjugate cRGD (R8–cRGD), and polyethylene glycol (PEG) were introduced into low-molecular-weight polyethyleneimine (LMW PEI) to form cRGD–R9–cholesterol–PEI–PEG (RRCPP) nanoparticles with specific targeting and highly penetrating abilities. The enhanced siRNA uptake efficiency of the RRCPP delivery system benefited from R8–cRGD modification. Wee1 is an oncogenic nuclear kinase that can regulate the cell cycle as a crucial G2/M checkpoint. Overexpression of Wee1 in melanoma may lead to a poor prognosis. In the present study, RRCPP nanoparticles were designed for Wee1 siRNA delivery to form an RRCPP/siWee1 complex, which significantly silenced the expression of the WEE1 gene (>60% inhibition) and induced B16 tumor cell apoptosis by abrogating the G2M checkpoint and DNA damage in vitro. Furthermore, the RRCPP/siWee1 complex suppressed B16 tumor growth in a subcutaneous xenograft model (nearly 85% inhibition rate) and lung metastasis (nearly 66% inhibition rate) with ideal in vivo safety. Briefly, our results support the validity of RRCPP as a potential Wee1 siRNA carrier for melanoma gene therapy.
中文翻译：
通过纳米偶联物递送的 Wee1 siRNA 治疗黑色素瘤
迄今为止，基于小干扰 RNA (siRNA) 的药物在癌症基因治疗中显示出巨大的潜力。尽管在 siRNA 设计和制造方面付出了相当大的努力，但不令人满意的递送系统仍然是基于 siRNA 的药物应用的限制。在这项工作中，胆固醇、细胞穿透肽偶联物 cRGD (R8-cRGD) 和聚乙二醇 (PEG) 被引入到低分子量聚乙烯亚胺 (LMW PEI) 中形成 cRGD-R9-胆固醇-PEI-PEG。 RRCPP) 纳米粒子具有特定的靶向性和高穿透能力。RRCPP 递送系统提高的 siRNA 摄取效率得益于 R8-cRGD 修饰。Wee1 是一种致癌核激酶，可以作为关键的 G2/M 检查点调节细胞周期。Wee1 在黑色素瘤中的过度表达可能导致预后不良。在目前的研究中，WEE1基因（>60% 抑制）并通过消除 G2M 检查点和体外DNA 损伤诱导 B16 肿瘤细胞凋亡。此外，RRCPP/siWee1 复合物在皮下异种移植模型中抑制 B16 肿瘤生长（抑制率接近 85%）和肺转移（抑制率接近 66%），具有理想的体内安全性。简而言之，我们的结果支持 RRCPP 作为黑色素瘤基因治疗的潜在 Wee1 siRNA 载体的有效性。
更新日期：2021-09-06
中文翻译：
通过纳米偶联物递送的 Wee1 siRNA 治疗黑色素瘤
迄今为止，基于小干扰 RNA (siRNA) 的药物在癌症基因治疗中显示出巨大的潜力。尽管在 siRNA 设计和制造方面付出了相当大的努力，但不令人满意的递送系统仍然是基于 siRNA 的药物应用的限制。在这项工作中，胆固醇、细胞穿透肽偶联物 cRGD (R8-cRGD) 和聚乙二醇 (PEG) 被引入到低分子量聚乙烯亚胺 (LMW PEI) 中形成 cRGD-R9-胆固醇-PEI-PEG。 RRCPP) 纳米粒子具有特定的靶向性和高穿透能力。RRCPP 递送系统提高的 siRNA 摄取效率得益于 R8-cRGD 修饰。Wee1 是一种致癌核激酶，可以作为关键的 G2/M 检查点调节细胞周期。Wee1 在黑色素瘤中的过度表达可能导致预后不良。在目前的研究中，WEE1基因（>60% 抑制）并通过消除 G2M 检查点和体外DNA 损伤诱导 B16 肿瘤细胞凋亡。此外，RRCPP/siWee1 复合物在皮下异种移植模型中抑制 B16 肿瘤生长（抑制率接近 85%）和肺转移（抑制率接近 66%），具有理想的体内安全性。简而言之，我们的结果支持 RRCPP 作为黑色素瘤基因治疗的潜在 Wee1 siRNA 载体的有效性。
京公网安备 11010802027423号