Camorani Simona, Cerchia Laura
Istituto per l'Endocrinologia e l'Oncologia Sperimentale "G. Salvatore", CNR, Via S. Pansini 5, 80131 Naples, Italy.
Cent Nerv Syst Agents Med Chem. 2015;15(2):126-37. doi: 10.2174/1871524915666150430122525.
Malignant glioma is the most prevalent and lethal primary brain tumor. Due to molecular heterogeneity and organ-specific clinical manifestations, it is essential to improve glioma treatment by shifting from conventional cytotoxic chemotherapy to more targeted therapies. Hence, innovative approaches based on ligands able to specifically detect and measure mutated proteins associated to a specific tumor phenotype are needed in order to refine diagnosis and therapy of glioma. To date, antibody- based approaches have been developed for in vivo applications but, in most cases, they show toxicity, do not reach adequate sensitivity and have a low permeability across the blood-brain-barrier. Single-stranded nucleic acid aptamers, generated by the SELEX (Systematic Evolution of Ligands by EXponential enrichment) process, have been shown as a valuable alternative to protein antibodies because may couple the advantages of their chemical nature to the high specific binding of antibodies to their proper targets. The simplicity of aptamers selection and derivatization with other molecules (nanocarriers, tracers for imaging, drugs) combined to low immunogenicity and toxicity, render them a versatile tool for identification of new biomarkers, in vitro diagnosis, in vivo imaging and targeted therapy. Aim of this review article is to discuss contemporary applications of aptamers as innovative tools for glioma diagnosis and therapy. We will describe promising new approaches for the identification of aptamers targeting proteins with a crucial role in glioma, including SELEX protocols against living glioma cells and brain tumor-initiating cells. Additionally, we will review recently proposed aptamer-based strategies for site-targeted controlled delivery of therapeutics and imaging agents to the brain. Summarizing, we hope that this article will provide an updated overview of perspectives and challenges for aptamer-based glioma treatment in the near future.
恶性胶质瘤是最常见且致命的原发性脑肿瘤。由于分子异质性和器官特异性临床表现，从传统的细胞毒性化疗转向更具针对性的疗法对于改善胶质瘤治疗至关重要。因此，需要基于能够特异性检测和测量与特定肿瘤表型相关的突变蛋白的配体的创新方法，以完善胶质瘤的诊断和治疗。迄今为止，已开发出基于抗体的体内应用方法，但在大多数情况下，它们显示出毒性，灵敏度不足且血脑屏障通透性低。通过指数富集配体系统进化（SELEX）过程产生的单链核酸适配体已被证明是蛋白质抗体的有价值替代品，因为它们可以将化学性质的优势与抗体对其适当靶标的高特异性结合相结合。适配体选择和与其他分子（纳米载体、成像示踪剂、药物）衍生化的简单性，再加上低免疫原性和毒性，使其成为鉴定新生物标志物、体外诊断、体内成像和靶向治疗的通用工具。这篇综述文章的目的是讨论适配体作为胶质瘤诊断和治疗创新工具的当代应用。我们将描述识别对胶质瘤起关键作用的靶向蛋白质的适配体的有前景的新方法，包括针对活胶质瘤细胞和脑肿瘤起始细胞的SELEX方案。此外，我们将综述最近提出的基于适配体的将治疗剂和成像剂靶向递送至脑的策略。总之，我们希望本文能提供关于基于适配体的胶质瘤治疗在不久的将来的前景和挑战的最新概述。
