Miller-Kleinhenz Jasmine M, Bozeman Erica N, Yang Lily
Winship Cancer Institute, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2015 Nov-Dec;7(6):797-816. doi: 10.1002/wnan.1343. Epub 2015 May 12.
Effective treatment of triple-negative breast cancer (TNBC) with its aggressive tumor biology, highly heterogeneous tumor cells, and poor prognosis requires an integrated therapeutic approach that addresses critical issues in cancer therapy. Multifunctional nanoparticles with the abilities of targeted drug delivery and noninvasive imaging for monitoring drug delivery and responses to therapy, such as theranostic nanoparticles, hold great promise toward the development of novel therapeutic approaches for the treatment of TNBC using a single therapeutic platform. The biological and pathological characteristics of TNBC provide insight into several potential molecular targets for current and future nanoparticle-based therapeutics. Extensive tumor stroma, highly proliferative cells, and a high rate of drug resistance are all barriers that must be appropriately addressed in order for these nanotherapeutic platforms to be effective. Utilization of the enhanced permeability and retention effect coupled with active targeting of cell surface receptors expressed by TNBC cells, and tumor-associated endothelial cells, stromal fibroblasts, and macrophages is likely to overcome such barriers to facilitate more effective drug delivery. An in-depth summary of current studies investigating targeted nanoparticles in preclinical TNBC mouse and human xenograft models is presented. This review aims to outline the current status of nanotherapeutic options for TNBC patients, identification of promising molecular targets, challenges associated with the development of targeted nanotherapeutics, the research done by our group as well as by others, and future perspectives on the nanomedicine field and ways to translate current preclinical studies into the clinic.
三阴性乳腺癌(TNBC)具有侵袭性的肿瘤生物学特性、高度异质性的肿瘤细胞且预后较差,对其进行有效治疗需要一种综合治疗方法,以解决癌症治疗中的关键问题。具有靶向药物递送和无创成像能力以监测药物递送及治疗反应的多功能纳米颗粒,如诊疗纳米颗粒,在利用单一治疗平台开发TNBC新型治疗方法方面具有巨大潜力。TNBC的生物学和病理学特征为当前及未来基于纳米颗粒的治疗提供了几个潜在的分子靶点。广泛的肿瘤基质、高增殖性细胞和高耐药率都是这些纳米治疗平台要想有效就必须妥善解决的障碍。利用增强的渗透和滞留效应,结合对TNBC细胞、肿瘤相关内皮细胞、基质成纤维细胞和巨噬细胞表达的细胞表面受体的主动靶向,可能会克服这些障碍,以促进更有效的药物递送。本文深入总结了目前在临床前TNBC小鼠和人异种移植模型中研究靶向纳米颗粒的相关研究。本综述旨在概述TNBC患者纳米治疗选择的现状、有前景的分子靶点的识别、靶向纳米治疗开发相关的挑战、我们团队及其他团队所做的研究,以及纳米医学领域的未来展望和将当前临床前研究转化为临床应用的方法。