Targeted nanoparticles for image-guided treatment of triple-negative breast cancer: clinical significance and technological advances.
Targeted nanoparticles for image-guided treatment of triple-negative breast cancer: clinical significance and technological advances.
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DOI：
10.1002/wnan.1343
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发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Yang L
中科院分区：
文献类型：
--
作者：
Miller-Kleinhenz JM;Bozeman EN;Yang L
三阴性乳腺癌（TNBC）具有侵袭性肿瘤生物学、高度异质性肿瘤细胞和不良预后，其有效治疗需要解决癌症治疗中关键问题的综合治疗方法。具有靶向药物递送和用于监测药物递送和对治疗的反应的非侵入性成像的能力的多功能纳米颗粒，例如治疗诊断纳米颗粒，对于开发使用单一治疗平台治疗TNBC的新型治疗方法具有很大的希望。TNBC的生物学和病理学特征为当前和未来的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、高度增殖的细胞和高耐药性率都是必须适当解决的障碍，以便这些纳米平台有效。利用增强的渗透性和滞留（EPR）效应，结合TNBC细胞和肿瘤相关内皮细胞、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，可能克服这些障碍以促进更有效的药物递送。深入总结了目前在临床前TNBC小鼠和人类异种移植模型中研究靶向纳米颗粒的研究。本综述旨在概述TNBC患者的纳米药物选择的现状，确定有前途的分子靶点，与靶向纳米治疗药物开发相关的挑战，我们小组以及其他人所做的研究以及纳米医学领域的未来前景，以及将当前临床前研究转化为临床的方法。
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 non-invasive imaging for monitoring drug delivery and responses to therapy, such as theranostic nanoparticles, hold great promise towards 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 (EPR) 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 others and future perspectives on the nanomedicine field and ways to translate current preclinical studies into the clinic.