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Nanoparticles containing a combination of a drug and an antibody for the treatment of breast cancer brain metastases

Wyatt, Emily A. and Davis, Mark E. (2020) Nanoparticles containing a combination of a drug and an antibody for the treatment of breast cancer brain metastases. Molecular Pharmaceutics, 17 (2). pp. 717-721. ISSN 1543-8384. PMCID PMC7061347 . doi:10.1021/acs.molpharmaceut.9b01167. https://resolver.caltech.edu/CaltechAUTHORS:20200109-143243224

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Abstract

In women with human epidermal growth factor 2 (HER2)-positive breast cancer, the improved control of systemic disease with new therapies has unmasked brain metastases that historically would have remained clinically silent. The efficacy of therapeutic agents against brain metastases is limited by their inability to permeate the blood–brain and blood–tumor barriers (BBB and BTB) in therapeutic amounts. Here, we investigate the potential of mucic acid-based, targeted nanoparticles designed to transcytose the BBB/BTB to deliver a small molecule drug, camptothecin (CPT), and therapeutic antibody, Herceptin, to brain metastases in mice. Treatment with BBB-targeted combination CPT/Herceptin nanoparticles significantly inhibits tumor growth compared to free CPT/Herceptin and BBB-targeted nanoparticles carrying CPT alone. Though not as efficacious, BBB-targeted nanoparticles carrying only Herceptin also elicit considerable antitumor activity. These results demonstrate the potential of the targeted nanoparticle system for the delivery of an antibody alone or in combination with other drugs across the BBB/BTB to improve the therapeutic outcome.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1021/acs.molpharmaceut.9b01167DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7061347/PubMed CentralArticle
ORCID:
AuthorORCID
Wyatt, Emily A.0000-0002-7534-0582
Davis, Mark E.0000-0001-8294-1477
Additional Information:© 2020 American Chemical Society. Received: November 12, 2019; Revised: January 6, 2020; Accepted: January 9, 2020; Published: January 9, 2020. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program (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 the research. E.A.W. performed the research. E.A.W. and M.E.D. analyzed data, and E.A.W. and M.E.D. wrote the paper. The authors declare no competing financial interest.
Funders:
Funding AgencyGrant Number
NSF Graduate Research FellowshipDGE-1745301
NIHCA 151819
Subject Keywords:polymeric nanoparticle; blood-brain barrier; systemic delivery; Herceptin; camptothecin
Issue or Number:2
PubMed Central ID:PMC7061347
DOI:10.1021/acs.molpharmaceut.9b01167
Record Number:CaltechAUTHORS:20200109-143243224
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200109-143243224
Official Citation:Nanoparticles Containing a Combination of a Drug and an Antibody for the Treatment of Breast Cancer Brain Metastases. Emily A. Wyatt and Mark E. Davis. Molecular Pharmaceutics 2020 17 (2), 717-721; DOI: 10.1021/acs.molpharmaceut.9b01167
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:100604
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:10 Jan 2020 15:16
Last Modified:16 Nov 2021 17:55

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