Poly(ethylene oxide)-block-polyphosphester-based Paclitaxel Conjugates as a Platform for Ultra-high Paclitaxel-loaded Multifunctional Nanoparticles. Academic Article uri icon

abstract

  • A new type of degradable, nanoscopic polymer assembly containing ultra-high levels of drug loading via covalent attachment within amphiphilic core-shell nanoparticle morphology has been generated as a potentially effective and safe anti-cancer agent. Poly(ethylene oxide)-block-polyphosphoester-based paclitaxel drug conjugates (PEO-b-PPE-g-PTX) were synthesized by rapid, scalable and versatile approach that involves only two steps: organocatalyst-promoted ring-opening-polymerization followed by click reaction-based conjugation of a PTX prodrug. Variations in the polymer-to-PTX stoichiometries allowed for optimization of the conjugation efficiency, the PTX drug loading and the resulting water solubilities of the entire polymer and the PTX content. The PEO-b-PPE-g-PTX formed well-defined micelles in aqueous solution, with a PTX loading capacity as high as 65 wt%, and a maximum PTX concentration of 6.2 mg/mL in water, which is 25000-fold higher than the aqueous solubility of free PTX. The positive cell-killing activity of PEO-b-PPE-g-PTX against several cancer cell lines is demonstrated, and the presence of pendant reactive functionality provides a powerful platform for future work to involve conjugation of multiple drugs and imaging agents to achieve chemotherapy and bioimaging.

published proceedings

  • Chem Sci

altmetric score

  • 3

author list (cited authors)

  • Zhang, S., Zou, J., Elsabahy, M., Karwa, A., Li, A., Moore, D. A., Dorshow, R. B., & Wooley, K. L.

citation count

  • 109

complete list of authors

  • Zhang, Shiyi||Zou, Jiong||Elsabahy, Mahmoud||Karwa, Amolkumar||Li, Ang||Moore, Dennis A||Dorshow, Richard B||Wooley, Karen L

publication date

  • January 2013