Marshall Morgan L, Wagstaff Kylie M
Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
Front Pharmacol. 2020 Jul 24;11:1115. doi: 10.3389/fphar.2020.01115. eCollection 2020.
Despite major advances, cancer remains one of the largest burdens of disease worldwide. One reason behind this is that killing tumor cells without affecting healthy surrounding tissue remains a largely elusive prospect, despite the widespread availability of cytotoxic chemotherapeutic agents. To meet these modern healthcare requirements, it is essential to develop precision therapeutics that minimise off-target side-effects for various cancer types. To this end, highly specific molecular targeting agents against cancer are of great interest. These agents may work by targeting intracellular signalling pathways following receptor binding, or internalization and targeting to specific subcellular compartments. DNA aptamers represent a promising molecular tool in this arena that can be used for both specific cell surface targeting and subsequent internalization and can also elicit a functional effect upon internalization. This review examines various cancer targeting cell-internalizing aptamers, with a particular focus towards functional aptamers that do not require additional conjugation to nanoparticles or small molecules to elicit a biological response. With a deeper understanding and precise exploitation of cancer specific molecular pathways, functional intracellular DNA aptamers may be a powerful step towards more widespread development of precision therapeutics.
尽管取得了重大进展,但癌症仍然是全球最大的疾病负担之一。其背后的一个原因是,尽管细胞毒性化疗药物广泛可得,但在不影响周围健康组织的情况下杀死肿瘤细胞在很大程度上仍然是一个难以实现的目标。为了满足现代医疗保健的这些要求,开发能够将各种癌症类型的脱靶副作用降至最低的精准疗法至关重要。为此,针对癌症的高度特异性分子靶向剂备受关注。这些药物可能通过在受体结合后靶向细胞内信号通路,或通过内化并靶向特定的亚细胞区室来发挥作用。DNA适配体是这一领域中一种很有前景的分子工具,可用于特异性细胞表面靶向以及随后的内化,并且在内化后还能引发功能效应。本文综述了各种靶向癌症的细胞内化适配体,特别关注那些不需要与纳米颗粒或小分子进行额外缀合就能引发生物学反应的功能性适配体。随着对癌症特异性分子途径的更深入理解和精确利用,功能性细胞内DNA适配体可能是朝着更广泛地开发精准疗法迈出的有力一步。