TY - JOUR
T1 - Sequential deconstruction of composite drug transport in metastatic breast cancer
AU - Goel, Shreya
AU - Zhang, Guodong
AU - Dogra, Prashant
AU - Nizzero, Sara
AU - Cristini, Vittorio
AU - Wang, Zhihui
AU - Hu, Zhenhua
AU - Li, Zheng
AU - Liu, Xuewu
AU - Shen, Haifa
AU - Ferrari, Mauro
N1 - Funding Information:
This work was partially supported by NIH grants U54CA210181, R01CA193880, R01CA222959, U01CA196403, U01CA213759, R01CA226537, and R01CA222007; U.S. Department of Defense grant W81XWH-17-1-0389; National Science Foundation grants DMS-1716737 and DMS-1930583; and the Ernest Cockrell Jr. Presidential Distinguished Chair.
Publisher Copyright:
Copyright © 2020 The Authors, some rights reserved.
PY - 2020/6
Y1 - 2020/6
N2 - 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.
AB - 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.
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U2 - 10.1126/sciadv.aba4498
DO - 10.1126/sciadv.aba4498
M3 - Article
C2 - 32637609
AN - SCOPUS:85087482357
VL - 6
SP - eaba4498
JO - Sci Adv
JF - Sci Adv
SN - 2375-2548
IS - 26
M1 - eaba4498
ER -