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

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 mo...

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Autores principales: Forder, James, Smith, Mallory, Wagner, Margot, Schaefer, Rachel J., Gorky, Jonathon, van Golen, Kenneth L., Nohe, Anja, Dhurjati, Prasad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853145/
https://www.ncbi.nlm.nih.gov/pubmed/31305024
http://dx.doi.org/10.1111/cts.12664
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author Forder, James
Smith, Mallory
Wagner, Margot
Schaefer, Rachel J.
Gorky, Jonathon
van Golen, Kenneth L.
Nohe, Anja
Dhurjati, Prasad
author_facet Forder, James
Smith, Mallory
Wagner, Margot
Schaefer, Rachel J.
Gorky, Jonathon
van Golen, Kenneth L.
Nohe, Anja
Dhurjati, Prasad
author_sort Forder, James
collection PubMed
description 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.
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spelling pubmed-68531452019-12-16 A Physiologically‐Based Pharmacokinetic Model for Targeting Calcitriol‐Conjugated Quantum Dots to Inflammatory Breast Cancer Cells Forder, James Smith, Mallory Wagner, Margot Schaefer, Rachel J. Gorky, Jonathon van Golen, Kenneth L. Nohe, Anja Dhurjati, Prasad Clin Transl Sci Research 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. John Wiley and Sons Inc. 2019-07-15 2019-11 /pmc/articles/PMC6853145/ /pubmed/31305024 http://dx.doi.org/10.1111/cts.12664 Text en © 2019 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research
Forder, James
Smith, Mallory
Wagner, Margot
Schaefer, Rachel J.
Gorky, Jonathon
van Golen, Kenneth L.
Nohe, Anja
Dhurjati, Prasad
A Physiologically‐Based Pharmacokinetic Model for Targeting Calcitriol‐Conjugated Quantum Dots to Inflammatory Breast Cancer Cells
title A Physiologically‐Based Pharmacokinetic Model for Targeting Calcitriol‐Conjugated Quantum Dots to Inflammatory Breast Cancer Cells
title_full A Physiologically‐Based Pharmacokinetic Model for Targeting Calcitriol‐Conjugated Quantum Dots to Inflammatory Breast Cancer Cells
title_fullStr A Physiologically‐Based Pharmacokinetic Model for Targeting Calcitriol‐Conjugated Quantum Dots to Inflammatory Breast Cancer Cells
title_full_unstemmed A Physiologically‐Based Pharmacokinetic Model for Targeting Calcitriol‐Conjugated Quantum Dots to Inflammatory Breast Cancer Cells
title_short A Physiologically‐Based Pharmacokinetic Model for Targeting Calcitriol‐Conjugated Quantum Dots to Inflammatory Breast Cancer Cells
title_sort physiologically‐based pharmacokinetic model for targeting calcitriol‐conjugated quantum dots to inflammatory breast cancer cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853145/
https://www.ncbi.nlm.nih.gov/pubmed/31305024
http://dx.doi.org/10.1111/cts.12664
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