Tumor-targeted gene delivery using molecularly engineered hybrid polymers functionalized with a tumor-homing peptide
Tumor-targeted gene delivery using molecularly engineered hybrid polymers functionalized with a tumor-homing peptide
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DOI：
10.1021/bc700408r
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发表时间：
2008-02-01
影响因子：
4.7
通讯作者：
Hammond, Paula T.
中科院分区：
文献类型：
--
作者：
Wood, Kris C.;Azarin, Samira M.;Hammond, Paula T.
在基因治疗可以用于临床设置，安全和有效的DNA递送系统必须开发，以克服一系列的细胞外和细胞内的运输障碍。作为一个模块化的，多功能的基因传递系统，以克服这些不同的障碍的发展的一步，我们已经开发了一个家庭的线性树枝状的“杂交”聚合物，其中包含组织靶向，非特异性相互作用，内体缓冲，和DNA结合的功能。在这里，我们展示了快速的三步，室温，水合成的混合聚合物，以及这些聚合物的功能化与肽靶向配体，特异性结合到葡萄糖调节蛋白-78 kDa（GRP-78），临床相关的肿瘤抗原在人类癌症患者中确定。这些聚合物系统可以将质粒DNA凝聚成小的纳米颗粒结构（
Before gene therapy can be used in clinical settings, safe and efficient DNA delivery systems must be developed to overcome a range of extra- and intracellular transport barriers. As a step toward the development of a modular, multifunctional gene delivery system to overcome these diverse barriers, we have developed a family of linear-dendritic "hybrid" polymers which contain functionalities for tissue targeting, minimization of nonspecific interactions, endosomal buffering, and DNA binding. Here, we demonstrate the rapid three-step, room-temperature, aqueous synthesis of hybrid polymers, as well as the functionalization of these polymers with a peptide targeting ligand that specifically binds to glucose-regulated protein-78 kDa (GRP-78), a clinically relevant tumor antigen identified in human cancer patients. These polymer systems can condense plasmid DNA into small nanoparticle structures (