The extraordinary boost in the understanding of the genetic and epigenetic mechanisms underlying the development and progression of different types of cancer, is offering an unprecedented hope for the development of precise therapeutics able to interfere or replace the expression of target genes. In the last decade, the design of stable, safe and effective RNA-based therapeutics has been significantly improved increasing the number of molecules now in preclinical or in clinical trials for cancer gene therapy. However, with few exclusions as liver and hematological malignancies which are easy accessible to drugs, the development of effective systemic approaches for the delivery of RNA therapeutics to target cells is still unmet. To be effective, targeting carriers must be able to overcome both functional and physical barriers to safely carry and accumulate the therapeutic through the organism selectively to the tumor site, penetrate the target cancer mass, promote the uptake and localization in the appropriate intracellular compartment ultimately leading to the effective modulation of gene expression. Nucleic acid aptamers are folded single stranded oligonucleotides that bind at high affinity and high specificity their targets (proteins, lipids, small molecules etc), coupling the advantages of binding specificity proper of antibodies to the chemical nature of nucleic acids, sometimes also termed “nucleic acid antibodies”. In several cases, aptamers targeting cell surface receptors are recycled into the cell together with the bound receptor enabling to drive conjugated therapeutics to cancer cells in a receptor-dependent manner. Therefore, besides other in vivo delivery strategies, the use of aptamers as precise and effective targeting moieties for anticancer RNA-based therapeutics has rapidly emerged and has been successfully addressed by several laboratories. In this Review, we will focus on the most recent and challenging progresses in the field that highlights the precision and flexibility of aptamer-based chimeras paving the way to the development of safe and effective carriers for cancer gene therapeutics.

对不同类型癌症的发生和发展所基于的遗传和表观遗传机制的理解的极大提高，为开发能够干扰或替代靶基因表达的精确疗法提供了前所未有的希望。在过去的十年中，稳定，安全和有效的基于RNA的治疗剂的设计已得到显着改善，从而增加了目前在癌症基因治疗的临床前或临床试验中的分子数量。然而，由于肝和血液系统恶性肿瘤几乎不易被药物排斥，因此尚未有效开发将RNA治疗药物递送至靶细胞的有效全身方法。为了有效，靶向载体必须能够克服功能性和物理性障碍，以安全地通过生物体将治疗剂安全地选择性地携带和积累到肿瘤部位，穿透靶标癌症块，促进在适当的细胞内区室的摄取和定位，最终导致有效的调节基因表达 核酸适体是折叠的单链寡核苷酸，它们以高亲和力和高特异性结合其靶标（蛋白质，脂质，小分子等），将抗体固有的结合特异性的优势与核酸的化学性质相结合，有时也称为“核酸”酸性抗体”。在某些情况下，靶向细胞表面受体的适体与结合的受体一起再循环到细胞中，从而能够以受体依赖的方式将缀合的治疗剂驱动至癌细胞。因此，除了其他在体内递送策略中，适配子作为基于抗癌RNA的治疗剂的精确有效的靶向部分的使用已迅速出现，并已被多个实验室成功解决。在本综述中，我们将重点关注该领域的最新进展和具有挑战性的进展，这些进展突出了基于适体的嵌合体的精确性和灵活性，为开发安全有效的癌症基因治疗剂载体铺平了道路。