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Method of establishing breast cancer brain metastases affects brain uptake and efficacy of targeted, therapeutic nanoparticles

Wyatt, Emily A. and Davis, Mark E. (2019) Method of establishing breast cancer brain metastases affects brain uptake and efficacy of targeted, therapeutic nanoparticles. Bioengineering & Translational Medicine, 4 (1). pp. 30-37. ISSN 2380-6761. PMCID PMC6336738. http://resolver.caltech.edu/CaltechAUTHORS:20180806-125608962

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Abstract

HER2‐targeted therapies effectively control systemic disease, but their efficacy against brain metastases is hindered by their low penetration of the blood‐brain and blood‐tumor barriers (BBB and BTB). We investigate brain uptake and antitumor efficacy of transferrin receptor (TfR)‐targeted, therapeutic nanoparticles designed to transcytose the BBB/BTB in three murine models. Two known models involving intracranial (IC) or intracardiac (ICD) injection of human breast cancer cells were employed, as was a third model developed here involving intravenous (IV) injection of the cells to form whole‐body tumors that eventually metastasize to the brain. We show the method of establishing brain metastases significantly affects therapeutic BBB/BTB penetration. Free drug accumulates and delays growth in IC‐ and ICD‐formed brain tumors, while non‐targeted nanoparticles show uptake and inhibition only in IC‐established metastases. TfR‐targeted nanoparticles accumulate and significantly delay growth in all three models, suggesting the IV model maintains a more intact BBB/BTB than the other models.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1002/btm2.10108DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336738PubMed CentralArticle
ORCID:
AuthorORCID
Wyatt, Emily A.0000-0002-7534-0582
Davis, Mark E.0000-0001-8294-1477
Additional Information:© 2018 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals, Inc. on behalf of The American Institute of Chemical Engineers. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Issue Online: 17 January 2019; Version of Record online: 05 November 2018; Accepted manuscript online: 06 August 2018; Manuscript accepted: 30 July 2018; Manuscript revised: 28 July 2018; Manuscript received: 07 June 2018. We thank Audrey Lee‐Gosselin for her assistance with intracranial injections, Xiaowei Zhang for his help in establishing MRI acquisition parameters and Mikhail Shapiro for access to the MRI facility. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. (DGE‐1745301; to E.A.W.). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. This work was supported by the National Cancer Institute Grant CA 151819. Author Contributions: E.A.W. and M.E.D. designed research; E.A.W. performed research; E.A.W. and M.E.D. analyzed data; and E.A.W. and M.E.D. wrote the paper.
Funders:
Funding AgencyGrant Number
NSF Graduate Research FellowshipDGE‐1745301
NIHCA 151819
Subject Keywords:blood-brain barrier, therapeutic delivery, brain metastasis, breast cancer, nanoparticle
PubMed Central ID:PMC6336738
Record Number:CaltechAUTHORS:20180806-125608962
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20180806-125608962
Official Citation:Wyatt EA, Davis ME. Method of establishing breast cancer brain metastases affects brain uptake and efficacy of targeted, therapeutic nanoparticles. Bioengineering & Translational Medicine. 2019;4:30–37. https://doi.org/10.1002/btm2.10108
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:88605
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:06 Aug 2018 22:00
Last Modified:28 Jan 2019 15:22

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