Modeling of nanotherapeutics delivery based on tumor perfusion.
Modeling of nanotherapeutics delivery based on tumor perfusion.
复制标题
基于肿瘤灌注的纳米治疗药物输送建模。
DOI：
10.1088/1367-2630/15/5/055004
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发表时间：
2013
影响因子：
3.3
通讯作者：
Frieboes,HermannB
中科院分区：
文献类型：
--
作者：
vandeVen,AnneL;Abdollahi,Behnaz;Martinez,CarlosJ;Burey,LaceyA;Landis,MelissaD;Chang,JennyC;Ferrari,Mauro;Frieboes,HermannB
实体肿瘤灌注的异质性阻碍了纳米治疗药物的最佳递送。用于获取患者特异性数据的临床成像方案已被证明难以实施。确定哪些灌注特征具有更大的预后价值，并将测量结果与血管结构和功能联系起来是具有挑战性的。随着系统给药纳米疗法的出现，其递送依赖于克服扩散和对流障碍来运输，这些知识变得越来越重要。我们描述了一个在单血管水平上测量血管灌注曲线的自动评估框架。从三阴性乳腺癌患者身上收集的原发肿瘤片段作为异种移植物在小鼠体内生长，注射荧光对比剂并使用活体显微镜进行监测。动脉峰值时间和静脉延迟时间这两个特征的概率分布直接来自于时间序列曲线，我们使用模糊c均值监督分类器对其进行分析，以便根据其灌注特征对单个肿瘤进行排序。由此得出的排名与实验纳米颗粒积累测量成反比，使纳米治疗药物输送的建模不需要任何关于组织结构或功能或其中包含的异质性的潜在假设。通过额外的校准，这些方法可以在各种肿瘤模型中研究纳米治疗药物的递送策略。
Heterogeneities in the perfusion of solid tumors prevent optimal delivery of nanotherapeutics. Clinical imaging protocols for obtaining patient-specific data have proven difficult to implement. It is challenging to determine which perfusion features hold greater prognostic value and to relate measurements to vessel structure and function. With the advent of systemically administered nanotherapeutics whose delivery is dependent on overcoming diffusive and convective barriers to transport, such knowledge is increasingly important. We describe a framework for the automated evaluation of vascular perfusion curves measured at the single vessel level. Primary tumor fragments, collected from triple-negative breast cancer patients and grown as xenografts in mice, were injected with fluorescence contrast and monitored using intravital microscopy. The time to arterial peak and venous delay, two features whose probability distributions were measured directly from time-series curves, were analyzed using a fuzzy c-mean supervised classifier in order to rank individual tumors according to their perfusion characteristics. The resulting rankings correlated inversely with experimental nanoparticle accumulation measurements, enabling the modeling of nanotherapeutics delivery without requiring any underlying assumptions about tissue structure or function, or heterogeneities contained therein. With additional calibration, these methodologies may enable the investigation of nanotherapeutics delivery strategies in a variety of tumor models.