Van den Avont Alexander, Sharma-Walia Neelam
Rosalind Franklin University of Medicine and Science, North Chicago, IL, United States.
Front Mol Biosci. 2023 Sep 21;10:1217769. doi: 10.3389/fmolb.2023.1217769. eCollection 2023.
Targeted therapy is highly desirable, as it allows for selective cytotoxicity on diseased cells without off-target side effects. Nucleolin is a remarkable target for cancer therapy given its high abundance, selective presence on the plasma membrane, and multifaceted influence on the initiation and progression of cancer. Nucleolin is a protein overexpressed on the cell membrane in many tumors and serves as a binding protein for several ligands implicated in angiogenesis and tumorigenesis. Nucleolin is present in the cytoplasm, nucleoplasm, and nucleolus and is used by selected pathogens for cell entry. AS1411 is a guanosine-rich oligonucleotide aptamer that binds nucleolin and is internalized in the tumor cells. AS1411 is well tolerated at therapeutic doses and localizes to tumor cells overexpressing nucleolin. AS1411 has a good safety profile with efficacy in relapsed acute myeloid leukemia and renal cell carcinoma producing mild or moderate side effects. The promising potential of AS1411 is its ability to be conjugated to drugs and nanoparticles. When a drug is bound to AS1411, the drug will localize to tumor cells leading to targeted therapy with fewer systemic side effects than traditional practices. AS1411 can also be bound to nanoparticles capable of detecting nucleolin at concentrations far lower than lab techniques used today for cancer diagnosis. AS1411 has a promising potential to change cancer diagnoses and treatment.
靶向治疗是非常理想的，因为它能够对病变细胞产生选择性细胞毒性，而不会产生脱靶副作用。鉴于核仁素在癌细胞中含量高、在质膜上选择性存在以及对癌症的起始和进展具有多方面影响，它是癌症治疗的一个显著靶点。核仁素是一种在许多肿瘤细胞膜上过度表达的蛋白质，并且作为几种与血管生成和肿瘤发生有关的配体的结合蛋白。核仁素存在于细胞质、核质和核仁中，并被某些病原体用于进入细胞。AS1411是一种富含鸟苷的寡核苷酸适配体，它能结合核仁素并被肿瘤细胞内化。AS1411在治疗剂量下耐受性良好，并定位于过度表达核仁素的肿瘤细胞。AS1411具有良好的安全性，对复发的急性髓系白血病和肾细胞癌有效，产生轻度或中度副作用。AS1411的有前景的潜力在于它能够与药物和纳米颗粒偶联。当一种药物与AS1411结合时，该药物将定位于肿瘤细胞，从而实现靶向治疗，与传统方法相比全身副作用更少。AS1411还可以与能够检测核仁素的纳米颗粒结合，其检测浓度远低于当今用于癌症诊断的实验室技术。AS1411在改变癌症诊断和治疗方面具有广阔的前景。
