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

• Published in: Clinical and translational science Vol. 12; no. 6; pp. 617 - 624
• Main Authors: Forder, James, Smith, Mallory, Wagner, Margot, Schaefer, Rachel J., Gorky, Jonathon, Golen, Kenneth L., Nohe, Anja, Dhurjati, Prasad
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.11.2019; John Wiley and Sons Inc; Wiley
• Subjects: 25-Hydroxyvitamin D; Animal tissues; Antibodies; Breast cancer; Calcitriol; Cancer therapies; Cell adhesion & migration; Cell cycle; Chemotherapy; Computer simulation; Inflammation; Medical prognosis; Medical research; Metastasis; Mucin; Pharmacokinetics; Quantum dots; Radiation therapy; Studies; Tumors; Vitamin D; Vitamin D3
• ISSN: 1752-8054; 1752-8062
• DOI: 10.1111/cts.12664

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.