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通过抑制口腔癌上皮-间质转化,Wnt-1小干扰RNA的纳米颗粒递送增强光动力疗法。

Nanoparticle delivery of Wnt-1 siRNA enhances photodynamic therapy by inhibiting epithelial-mesenchymal transition for oral cancer.

作者信息

Ma Chuan, Shi Leilei, Huang Yu, Shen Lingyue, Peng Hao, Zhu Xinyuan, Zhou Guoyu

机构信息

Ninth People's Hospital Affiliated to Shanghai Jiao Tong University Medical College, School of Stomatology, Department of Oral Maxillofacial Surgery, Shanghai Institute of Stomatology, Shanghai Key Point Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, P. R. China.

School of Chemistry and Chemical Engineering, Shanghai Key Lab of Electrical Insulation and Thermal Aging, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.

出版信息

Biomater Sci. 2017 Feb 28;5(3):494-501. doi: 10.1039/c6bm00833j.

DOI:10.1039/c6bm00833j
PMID:28070573
Abstract

Activation of the epithelial to mesenchymal transition (EMT) in photodynamic therapy (PDT) can lead to the recurrence and progression of tumors. To enhance the effects of PDT, it is essential to inhibit the Wnt/β-catenin signaling pathway involved in EMT progression. Herein, we used polyethylene glycol-polyethyleneimine-chlorin e6 (PEG-PEI-Ce6) nanoparticles to efficiently deliver Wnt-1 small interfering RNA (siRNA) to the cytoplasm of KB cells (oral squamous cell carcinoma) that were subjected to PDT. Wnt-1 siRNA effectively inhibited the Wnt/β-catenin signaling pathway, reducing the expression of Wnt-1, β-catenin and vimentin that are crucial to the EMT. Combined with Wnt-1 siRNA, PEG-PEI-Ce6 nanoparticle mediated PDT inhibited cell growth and enhanced the cancer cell killing effect remarkably. Our results show the promise of combination therapy of PEG-PEI-Ce6 nanoparticles for delivery of Wnt-1 siRNA along with PDT in the treatment of oral cancer.

摘要

光动力疗法(PDT)中上皮-间质转化(EMT)的激活可导致肿瘤复发和进展。为增强PDT效果,抑制参与EMT进程的Wnt/β-连环蛋白信号通路至关重要。在此,我们使用聚乙二醇-聚乙烯亚胺-二氢卟吩e6(PEG-PEI-Ce6)纳米颗粒,将Wnt-1小干扰RNA(siRNA)有效递送至接受PDT的KB细胞(口腔鳞状细胞癌)细胞质中。Wnt-1 siRNA有效抑制Wnt/β-连环蛋白信号通路,降低对EMT至关重要的Wnt-1、β-连环蛋白和波形蛋白的表达。与Wnt-1 siRNA联合使用时,PEG-PEI-Ce6纳米颗粒介导的PDT抑制细胞生长,并显著增强癌细胞杀伤效果。我们的结果显示了PEG-PEI-Ce6纳米颗粒联合递送Wnt-1 siRNA与PDT治疗口腔癌的前景。

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