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

Clin Transl Sci. 2019 Nov;12(6):617-624. doi: 10.1111/cts.12664. Epub 2019 Jul 15.

Abstract

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.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / immunology
  • Calcitriol / administration & dosage
  • Calcitriol / pharmacokinetics*
  • Cell Line, Tumor
  • Drug Delivery Systems / methods
  • Female
  • Humans
  • Immunoconjugates / administration & dosage
  • Immunoconjugates / pharmacokinetics
  • Mice
  • Models, Biological*
  • Mucin-1 / immunology
  • Quantum Dots / administration & dosage*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Immunoconjugates
  • MUC1 protein, human
  • Mucin-1
  • Calcitriol