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利用MUC1适配体靶向纳米颗粒用于乳腺癌的精准医疗。

Harnessing MUC1 aptamer-targeted nanoparticles for precision medicine in breast cancer.

作者信息

Khan Mohammad Sameer, Gupta Garima, Alsayari Abdulrhman, Wahab Shadma, Kesharwani Prashant

机构信息

Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.

Graphic Era Hill University, Dehradun 248002, India; School of Allied Medical Sciences, Lovely Professional University, Phagwara, Punjab, India.

出版信息

Int J Pharm. 2025 Jun 10;678:125721. doi: 10.1016/j.ijpharm.2025.125721. Epub 2025 May 11.

Abstract

Mucin 1 (MUC1) is a transmembrane glycoprotein from the mucin family, characterized by extensive glycosylation. It is present on the surface of most epithelial cells and is involved in interactions with invading microbes. Elevated MUC1 levels have been reported to affect multiple signaling pathways, influencing processes such as epithelial-mesenchymal transition in breast cancer, cellular metabolism, apoptosis, and distant metastasis. Inadequate glycosylation of MUC1 exposes new antigenic epitopes, presenting potential targets for diagnostic and therapeutic applications. Additionally, MUC1 is strongly linked to hypoxia-inducible factors (HIF), forming a positive feedback loop that promotes the advancement of hypoxic malignant tumors Recent advancements in targeted therapy have highlighted the potential of MUC1 aptamers, short nucleic acid sequences that bind with high affinity and specificity to MUC1, as promising therapeutic agents. Therapeutic strategies targeting MUC1 include monoclonal antibodies, antibody-drug conjugates, cancer vaccines, and aptamers, with several already advancing to clinical trial stages. The review explores the role and mechanisms of MUC1 aptamers in the biological functions of malignant tumors, emphasizing their potential in breast cancer therapy, diagnostic imaging, and aptamer-based biosensors. It also reviews clinical trials and discusses the future potential of MUC1 aptamer nanoparticles (NPs) for breast cancer treatment.

摘要

黏蛋白1(MUC1)是一种来自黏蛋白家族的跨膜糖蛋白,其特征在于广泛的糖基化。它存在于大多数上皮细胞表面,并参与与入侵微生物的相互作用。据报道,MUC1水平升高会影响多种信号通路,影响乳腺癌上皮-间质转化、细胞代谢、细胞凋亡和远处转移等过程。MUC1糖基化不足会暴露出新的抗原表位,为诊断和治疗应用提供潜在靶点。此外,MUC1与缺氧诱导因子(HIF)密切相关,形成一个促进缺氧恶性肿瘤进展的正反馈环。靶向治疗的最新进展突出了MUC1适配体(与MUC1具有高亲和力和特异性结合的短核酸序列)作为有前景的治疗药物的潜力。针对MUC1的治疗策略包括单克隆抗体、抗体-药物偶联物、癌症疫苗和适配体,其中几种已进入临床试验阶段。本综述探讨了MUC1适配体在恶性肿瘤生物学功能中的作用和机制,强调了它们在乳腺癌治疗、诊断成像和基于适配体的生物传感器方面的潜力。它还回顾了临床试验,并讨论了MUC1适配体纳米颗粒(NPs)在乳腺癌治疗中的未来潜力。

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