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序贯解构转移性乳腺癌中的复合药物转运。

Sequential deconstruction of composite drug transport in metastatic breast cancer.

机构信息

Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA.

Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, TX, USA.

出版信息

Sci Adv. 2020 Jun 24;6(26):eaba4498. doi: 10.1126/sciadv.aba4498. eCollection 2020 Jun.

DOI:10.1126/sciadv.aba4498
PMID:32637609
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7314527/
Abstract

It is challenging to design effective drug delivery systems (DDS) that target metastatic breast cancers (MBC) because of lack of competent imaging and image analysis protocols that suitably capture the interactions between DDS and metastatic lesions. Here, we integrate high temporal resolution of in vivo whole-body PET-CT, ex vivo whole-organ optical imaging, high spatial resolution of confocal microscopy, and mathematical modeling, to systematically deconstruct the trafficking of injectable nanoparticle generators encapsulated with polymeric doxorubicin (iNPG-pDox) in pulmonary MBC. iNPG-pDox accumulated substantially in metastatic lungs, compared to healthy lungs. Intratumoral distribution and retention of iNPG-pDox varied with lesion size, possibly induced by locally remodeled microenvironment. We further used multiscale imaging and mathematical simulations to provide improved drug delivery strategies for MBC. Our work presents a multidisciplinary translational toolbox to evaluate transport and interactions of DDS within metastases. This knowledge can be recursively applied to rationally design advanced therapies for metastatic cancers.

摘要

设计针对转移性乳腺癌（MBC）的有效药物递送系统（DDS）具有挑战性，因为缺乏合适的成像和图像分析协议来充分捕捉 DDS 与转移性病变之间的相互作用。在这里，我们整合了体内全身 PET-CT 的高时间分辨率、离体全器官光学成像、共聚焦显微镜的高空间分辨率和数学建模，以系统地解构包裹在聚合物阿霉素（iNPG-pDox）中的可注射纳米颗粒发生器（iNPG-pDox）在肺 MBC 中的转运。与健康肺相比，iNPG-pDox 在转移性肺中大量积累。iNPG-pDox 的肿瘤内分布和保留因局部重塑的微环境而随病变大小而变化。我们进一步使用多尺度成像和数学模拟为 MBC 提供了改进的药物输送策略。我们的工作提供了一个多学科转化工具包，用于评估 DDS 在转移灶内的传输和相互作用。这些知识可以递归地应用于合理设计转移性癌症的先进治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f33/7314527/32067a749d4e/aba4498-F6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f33/7314527/c322f0c55f06/aba4498-F1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f33/7314527/80d6735a22db/aba4498-F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f33/7314527/27a63059a540/aba4498-F5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f33/7314527/32067a749d4e/aba4498-F6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f33/7314527/c322f0c55f06/aba4498-F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f33/7314527/33d28e87dfda/aba4498-F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f33/7314527/dd994788d026/aba4498-F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f33/7314527/80d6735a22db/aba4498-F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f33/7314527/27a63059a540/aba4498-F5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f33/7314527/32067a749d4e/aba4498-F6.jpg

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