A Physiologically-Based Pharmacokinetic Model for Targeting Calcitriol-Conjugated Quantum Dots to Inflammatory Breast Cancer Cells.


Journal

Clinical and translational science
ISSN: 1752-8062
Titre abrégé: Clin Transl Sci
Pays: United States
ID NLM: 101474067

Informations de publication

Date de publication:
11 2019
Historique:
received: 26 04 2019
accepted: 17 05 2019
pubmed: 16 7 2019
medline: 1 9 2020
entrez: 16 7 2019
Statut: ppublish

Résumé

Quantum dots (QDs) conjugated with 1,25 dihydroxyvitamin D3 (calcitriol) and Mucin-1 (MUC-1) antibodies (SM3) have been found to target inflammatory breast cancer (IBC) tumors and reduce proliferation, migration, and differentiation of these tumors in mice. A physiologically-based pharmacokinetic model has been constructed and optimized to match experimental data for multiple QDs: control QDs, QDs conjugated with calcitriol, and QDs conjugated with both calcitriol and SM3 MUC1 antibodies. The model predicts continuous QD concentration for key tissues in mice distinguished by IBC stage (healthy, early-stage, and late-stage). Experimental and clinical efforts in QD treatment of IBC can be augmented by in silico simulations that predict the short-term and long-term behavior of QD treatment regimens.

Identifiants

pubmed: 31305024
doi: 10.1111/cts.12664
pmc: PMC6853145
doi:

Substances chimiques

Antineoplastic Agents 0
Immunoconjugates 0
MUC1 protein, human 0
Mucin-1 0
Calcitriol FXC9231JVH

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

617-624

Informations de copyright

© 2019 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.

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Auteurs

James Forder (J)

Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware, USA.

Mallory Smith (M)

Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware, USA.

Margot Wagner (M)

Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware, USA.

Rachel J Schaefer (RJ)

Biological Sciences, University of Delaware, Newark, Delaware, USA.

Jonathon Gorky (J)

Daniel Baugh Institute for Functional Genomics and Computational Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Kenneth L van Golen (KL)

Biological Sciences, University of Delaware, Newark, Delaware, USA.

Anja Nohe (A)

Biological Sciences, University of Delaware, Newark, Delaware, USA.

Prasad Dhurjati (P)

Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware, USA.

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Classifications MeSH