Aptamer-directed siRNA delivery systems for triple-negative breast cancer therapy.

IF 1.1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Dilpreet Singh, Satvir Singh, Nitin Tandon
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引用次数: 0

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the absence of estrogen, progesterone, and HER2 receptors, making it unresponsive to targeted hormonal and HER2-based therapies. Current treatment options, including chemotherapy and radiation, have limited efficacy and are associated with severe side effects, emphasizing the need for innovative therapeutic strategies. Aptamer-siRNA conjugates have emerged as a promising gene-silencing approach, leveraging the high specificity of nucleic acid aptamers to selectively deliver short interfering RNA (siRNA) to TNBC cells. Aptamers, single-stranded DNA or RNA molecules generated via SELEX, exhibit nanomolar-range binding affinities (Kd ∼0.5-2.5 nM) for TNBC biomarkers such as EGFR, EpCAM, nucleolin, and MUC1, enabling receptor-mediated internalization of siRNA. Preclinical studies have demonstrated that aptamer-siRNA conjugates enhance cellular uptake by 5-10-fold, improve gene silencing efficiency (80-95%), and extend siRNA stability in circulation (from <2 h to 6-9 h). In xenograft models, aptamer-siRNA therapies have shown tumor volume reductions of 60-85%, outperforming non-targeted siRNA and chemotherapy. However, challenges such as nuclease degradation, immune responses, endosomal escape, and large-scale production remain significant hurdles to clinical translation. Recent advances in chemical modifications, lipid-based carriers, and artificial intelligence-driven aptamer design are addressing these limitations, paving the way for personalized, precision RNAi-based therapeutics. This review explores the mechanisms, recent advancements, challenges, and future directions of aptamer-siRNA therapeutics, providing a comprehensive analysis of their potential to revolutionize TNBC treatment by offering targeted, effective, and less toxic gene-silencing approaches.

适配体定向siRNA递送系统用于三阴性乳腺癌治疗。
三阴性乳腺癌(TNBC)是一种侵袭性乳腺癌亚型,其特征是缺乏雌激素、孕激素和HER2受体,使其对靶向激素和HER2为基础的治疗无反应。目前的治疗方案,包括化疗和放疗,疗效有限,并伴有严重的副作用,强调需要创新的治疗策略。核酸适体-siRNA缀合物已成为一种很有前途的基因沉默方法,利用核酸适体的高特异性选择性地向TNBC细胞递送短干扰RNA (siRNA)。适配体是通过SELEX产生的单链DNA或RNA分子,对TNBC生物标志物(如EGFR、EpCAM、核蛋白和MUC1)具有纳米级的结合亲和力(Kd ~ 0.5-2.5 nM),使受体介导的siRNA内化成为可能。临床前研究表明,适体-siRNA偶联物可使细胞摄取提高5-10倍,提高基因沉默效率(80-95%),并延长siRNA在循环中的稳定性
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来源期刊
Nucleosides, Nucleotides & Nucleic Acids
Nucleosides, Nucleotides & Nucleic Acids 生物-生化与分子生物学
CiteScore
2.60
自引率
7.70%
发文量
91
审稿时长
6 months
期刊介绍: Nucleosides, Nucleotides & Nucleic Acids publishes research articles, short notices, and concise, critical reviews of related topics that focus on the chemistry and biology of nucleosides, nucleotides, and nucleic acids. Complete with experimental details, this all-inclusive journal emphasizes the synthesis, biological activities, new and improved synthetic methods, and significant observations related to new compounds.
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