Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, USA.
Biomaterials. 2012 Feb;33(6):1838-50. doi: 10.1016/j.biomaterials.2011.11.020. Epub 2011 Dec 3.
With the reason that systemically administered adenovirus (Ad) is rapidly extinguished by innate/adaptive immune responses and accumulation in liver, in vivo application of the Ad vector is strictly restricted. For achieving to develop successful Ad vector systems for cancer therapy, the chemical or physical modification of Ad vectors with polymers has been generally used as a promising strategy to overcome the obstacles. With polyethylene glycol (PEG) first in order, a variety of polymers have been developed to shield the surface of therapeutic Ad vectors and well accomplished to extend circulation time in blood and reduce liver toxicity. However, although polymer-coated Ads can successfully evacuate from a series of guarding systems in vivo and locate within tumors by enhanced permeability and retention (EPR) effect, the possibility to entering into the target cell is few and far between. To endow targeting moiety to polymer-coated Ad vectors, a diversity of ligands such as tumor-homing peptides, growth factors or antibodies, have been introduced with avoiding unwanted transduction and enhancing therapeutic efficacy. Here, we will describe and classify the characteristics of the published polymers with respect to Ad vectors. Furthermore, we will also compare the properties of variable targeting ligands, which are being utilized for addressing polymer-coated Ad vectors actively.
由于系统给予的腺病毒(Ad)会迅速被先天/适应性免疫反应所消除并在肝脏中积累,因此体内应用 Ad 载体受到严格限制。为了开发成功的用于癌症治疗的 Ad 载体系统,通常使用化学或物理修饰 Ad 载体与聚合物作为一种有前途的策略来克服这些障碍。以聚乙二醇(PEG)为例,已经开发了多种聚合物来屏蔽治疗性 Ad 载体的表面,并成功延长了在血液中的循环时间,降低了肝脏毒性。然而,尽管聚合物涂层的 Ads 可以成功地从体内的一系列保护系统中逃逸,并通过增强的渗透性和保留(EPR)效应定位在肿瘤内,但进入靶细胞的可能性很小。为了给聚合物涂层的 Ad 载体赋予靶向部分,已经引入了多种配体,如肿瘤归巢肽、生长因子或抗体,以避免不必要的转导并增强治疗效果。在这里,我们将描述和分类已发表的聚合物的特性,以及正在积极用于聚合物涂层的 Ad 载体的各种靶向配体的性质。