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.
Graphical Abstract
Animals with subcutaneous xenograft tumors are injected with encapsulated (non-covalently) drugs in iron-stabilized polymer micelles. At 24 h contrast in the tumor is identified by MRI, and although signal is cleared by 168 h, tumor growth is significantly inhibited by release of the API over time from the polymer micelle.
Funding: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number U43CA179468 and under Contract No. HHSN261201400018C.
Conflicts of Interest: The authors have no conflict of interest to declare.
