Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, 31080 Pamplona, Spain.
Int J Pharm. 2021 Mar 1;596:120291. doi: 10.1016/j.ijpharm.2021.120291. Epub 2021 Jan 29.
Lack of selectivity together with severe side effects in conventional cancer treatment have afforded the development of new strategies based on gene therapy. Nowadays, gene therapy is employed through both viral and non-viral vectors. In spite of the high transfection activity of viral vectors, some drawbacks have pointed out to non-viral vectors as a safer alternative. To overcome low efficiency as well as other issues associated with the use of non-viral vectors, complexes formed by lipids and polymers with DNA, named lipoplexes and polyplexes respectively, have been modified in order to improve its features. Suitability of cancer gene therapy also requires the capacity to distinguish between normal and tumoral cells. This requirement has been solved by the addition of specific ligands that enable receptor binding and subsequent endocytosis. In this article we review the most recent approaches in structure modification of non-viral vectors through different methods comprising conjugation, addition of helper lipids or changes in design and synthesis as well as the strategy based on exploiting receptors that are usually overexpressed in malignancies. Such improvements confer specificity, efficient gene delivery, condensation, protection of DNA and low levels of toxicity avoiding off-target effects which turn into a potential tool to treat cancer.
传统癌症治疗方法缺乏选择性且副作用严重，这促使人们开发了基于基因治疗的新策略。目前，基因治疗既可以通过病毒载体，也可以通过非病毒载体来实现。尽管病毒载体具有很高的转染活性，但一些缺点指出非病毒载体是一种更安全的选择。为了克服非病毒载体效率低下和其他相关问题，已经对与 DNA 形成复合物的脂质和聚合物（分别称为脂质体和聚合物体）进行了修饰，以改善其特性。癌症基因治疗的适用性还需要能够区分正常细胞和肿瘤细胞。通过添加能够进行受体结合和随后内吞作用的特定配体，可以解决这一要求。在本文中，我们综述了通过不同方法（包括缀合、添加辅助脂质或改变设计和合成）对非病毒载体进行结构修饰的最新方法，以及基于利用通常在恶性肿瘤中过度表达的受体的策略。这些改进赋予了特异性、高效的基因传递、浓缩、DNA 保护和低毒性水平，避免了脱靶效应，这使其成为治疗癌症的一种有潜力的工具。
