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用于将药物和基因递送至乳腺癌中以破坏Notch信号通路的纳米材料。

Nanomaterials for delivery of drugs and genes to disrupt notch signaling pathway in breast cancer.

作者信息

Gummadi Ramakrishna, Nori Lakshmi Prasanthi, Pindiprolu Sai Kiran S S, Dasari Nagasen, Ahmad Zubair, Km Muhasina

机构信息

School of Pharmacy, Aditya University, Surampalem, 533437, India.

Department of Pharmaceutics, Shri Vishnu College of Pharmacy, Bhimavaram, India.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 May 20. doi: 10.1007/s00210-025-04082-2.

Abstract

Breast cancer, marked by considerable heterogeneity and intricate molecular subgroups, poses substantial obstacles to therapy. Epithelial-mesenchymal transition (EMT) and the existence of tumor-initiating cells (TICs) facilitate treatment resistance, metastasis, and worse prognosis. The Notch signaling system has garnered significant interest for its involvement in promoting epithelial-mesenchymal transition (EMT), maintaining tumor-initiating cells (TIC), and facilitating cancer progression, especially in truculent subtypes such as triple-negative breast cancer (TNBC). Targeting the Notch system represents a promising therapeutic strategy; nevertheless, traditional inhibitors frequently encounter obstacles, including inadequate selectivity and bioavailability. Nanocarrier-based drug delivery systems provide novel therapeutic strategies to these difficulties by augmenting the targeted delivery of Notch inhibitors and enhancing therapeutic efficacy. Solid lipid nanoparticles (SLNs), polymeric nanoparticles, lipid-based nanocarriers, and micelles exhibit promise in delivering Notch inhibitors to neoplastic cells, altering the Notch signaling pathway, and surmounting drug resistance. This review examines recent breakthroughs in nanocarrier systems aimed at the Notch signaling pathway in breast cancer, highlighting the therapeutic potential of integrating nanomedicine with Notch inhibition to disrupt epithelial-mesenchymal transition (EMT), tumor-initiating cells (TICs), and metastasis, thereby enhancing clinical outcomes.

摘要

乳腺癌具有显著的异质性和复杂的分子亚群,给治疗带来了巨大障碍。上皮-间质转化(EMT)和肿瘤起始细胞(TICs)的存在促进了治疗抗性、转移并导致更差的预后。Notch信号系统因其参与促进上皮-间质转化(EMT)、维持肿瘤起始细胞(TIC)以及促进癌症进展而备受关注,尤其是在三阴性乳腺癌(TNBC)等侵袭性亚型中。靶向Notch系统是一种有前景的治疗策略;然而,传统抑制剂常常遇到障碍,包括选择性和生物利用度不足。基于纳米载体的药物递送系统通过增强Notch抑制剂的靶向递送和提高治疗效果,为这些难题提供了新的治疗策略。固体脂质纳米粒(SLNs)、聚合物纳米粒、基于脂质的纳米载体和胶束在将Notch抑制剂递送至肿瘤细胞、改变Notch信号通路以及克服耐药性方面展现出前景。本综述探讨了针对乳腺癌Notch信号通路的纳米载体系统的最新突破,强调了将纳米医学与Notch抑制相结合以破坏上皮-间质转化(EMT)、肿瘤起始细胞(TICs)和转移从而改善临床结果的治疗潜力。

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