Tumor associated macrophages act as a slow-release reservoir of nano-therapeutic Pt(IV) pro-drug

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Tumor associated macrophages act as a slow-release reservoir of nano-therapeutic Pt(IV) pro-drug

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Title: Tumor associated macrophages act as a slow-release reservoir of nano-therapeutic Pt(IV) pro-drug
Author: Miller, Miles A.; Zheng, Yao-Rong; Gadde, Suresh; Pfirschke, Christina; Zope, Harshal; Engblom, Camilla; Kohler, Rainer H.; Iwamoto, Yoshiko; Yang, Katherine S.; Askevold, Bjorn; Kolishetti, Nagesh; Pittet, Mikael; Lippard, Stephen J.; Farokhzad, Omid C.; Weissleder, Ralph

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Citation: Miller, M. A., Y. Zheng, S. Gadde, C. Pfirschke, H. Zope, C. Engblom, R. H. Kohler, et al. 2015. “Tumor associated macrophages act as a slow-release reservoir of nano-therapeutic Pt(IV) pro-drug.” Nature communications 6 (1): 8692. doi:10.1038/ncomms9692. http://dx.doi.org/10.1038/ncomms9692.
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Abstract: Therapeutic nanoparticles (TNPs) aim to deliver drugs more safely and effectively to cancers, yet clinical results have been unpredictable owing to limited in vivo understanding. Here we use single-cell imaging of intratumoral TNP pharmacokinetics and pharmacodynamics to better comprehend their heterogeneous behavior. Model TNPs comprised of a fluorescent platinum(IV) pro-drug and a clinically-tested polymer platform (PLGA-b-PEG) promote long drug circulation and alter accumulation by directing cellular uptake toward tumor associated macrophages (TAMs). Simultaneous imaging of TNP vehicle, its drug payload, and single-cell DNA damage response reveals that TAMs serve as a local drug depot that accumulates significant vehicle from which DNA damaging Pt payload gradually releases to neighboring tumor cells. Correspondingly, TAM depletion reduces intratumoral TNP accumulation and efficacy. Thus, nanotherapeutics co-opt TAMs for drug delivery, which has implications for TNP design and for selecting patients into trials.
Published Version: doi:10.1038/ncomms9692
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711745/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:26860152
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