Folate-Decorated Polyamidoamine Dendrimer Nanoparticles for Head and Neck Cancer Gene Therapy.
Folate-Decorated Polyamidoamine Dendrimer Nanoparticles for Head and Neck Cancer Gene Therapy.
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DOI：
10.1007/978-1-4939-9220-1_26
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发表时间：
2019
影响因子：
--
通讯作者：
Leyuan Xu;Hu Yang
中科院分区：
文献类型：
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作者：
Leyuan Xu;Hu Yang
基于树状大分子和许多其他类型的纳米颗粒载体的基因传递系统已经被开发出来，但很少有针对头颈部鳞状细胞癌（HNSCC）的基因传递系统。在这里，我们描述了设计和合成荧光标记的，叶酸修饰的聚酰胺胺（PAMAM）第4代（G4）树状大分子偶联物，用于hnscc靶向基因传递。该递送系统包括树状大分子作为载体，与叶酸（FA）结合作为HNSCC靶向部分，以及成像剂异硫氰酸荧光素（FITC）或IRDye 800CW （NIR）分别用于体外运输或生物成像。通过与质粒或siRNA络合，G4-FA/质粒（或siRNA）显著提高了HNSCC细胞的基因转染或敲低效率。在小鼠HNSCC异种移植模型中，这种多功能G4-FA载体表现出高生物相容性、肿瘤靶向性、高摄取和持续保留，使其成为HNSCC基因治疗的合适平台。
Gene delivery systems have been developed on the basis of dendrimers and many other types of nanoparticle carriers, but few have been developed for head and neck squamous cell carcinomas (HNSCC). Herein, we describe the design and synthesis of fluorescently labeled, folic acid-decorated polyamidoamine (PAMAM) generation 4 (G4) dendrimer conjugates for HNSCC-targeted gene delivery. This delivery system comprises a dendrimer as the carrier that is conjugated with folic acid (FA) as HNSCC targeting moiety and imaging agents fluorescein isothiocyanate (FITC) or IRDye 800CW (NIR) for in vitro trafficking or bioimaging, respectively. By complexing with plasmid or siRNA, G4-FA/plasmid (or siRNA) significantly enhances gene transfection or knockdown efficiency in HNSCC cells. In a mouse xenograft model of HNSCC, this versatile G4-FA vector shows high biocompatibility, tumor targeting, high uptake, and sustained retention, making it a suitable platform for HNSCC gene therapy.