1. Imaging the delivery of drug-loaded, iron-stabilized micelles.
- Author
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Bakewell SJ, Carie A, Costich TL, Sethuraman J, Semple JE, Sullivan B, Martinez GV, Dominguez-Viqueira W, and Sill KN
- Subjects
- Animals, Cell Line, Tumor, Drug Carriers pharmacokinetics, Female, Humans, Magnetic Resonance Imaging, Mice, Nude, Polymers chemistry, Rats, Sprague-Dawley, Xenograft Model Antitumor Assays, Antineoplastic Agents pharmacokinetics, Breast Neoplasms diagnostic imaging, Colorectal Neoplasms drug therapy, Drug Carriers chemistry, Iron chemistry, Micelles
- Abstract
Nanoparticle drug carriers hold potential to improve current cancer therapy by delivering payload to the tumor environment and decreasing toxic side effects. Challenges in nanotechnology drug delivery include plasma instability, site-specific delivery, and relevant biomarkers. We have developed a triblock polymer comprising a hydroxamic acid functionalized center block that chelates iron to form a stabilized micelle that physically entraps chemotherapeutic drugs in the hydrophobic core. The iron-imparted stability significantly improves the integrity of the micelle and extends circulation pharmacokinetics in plasma over that of free drug. Furthermore, the paramagnetic properties of the iron-crosslinking exhibits contrast in the tumors for imaging by magnetic resonance. Three separate nanoparticle formulations demonstrate improved anti-tumor efficacy in xenograft models and decreased toxicity. We report a stabilized polymer micelle that improves the tolerability and efficacy of chemotherapeutic drugs, and holds potential for non-invasive MRI to image drug delivery and deposition in the tumor., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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