Issue 5, 2013

Poly(ethylene oxide)-block-polyphosphester-based paclitaxel conjugates as a platform for ultra-high paclitaxel-loaded multifunctional nanoparticles

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 a 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−1 in water, which is 25 000-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.

Graphical abstract: Poly(ethylene oxide)-block-polyphosphester-based paclitaxel conjugates as a platform for ultra-high paclitaxel-loaded multifunctional nanoparticles

Supplementary files

Article information

Article type
Edge Article
Submitted
28 Jan 2013
Accepted
27 Feb 2013
First published
06 Mar 2013

Chem. Sci., 2013,4, 2122-2126

Poly(ethylene oxide)-block-polyphosphester-based paclitaxel conjugates as a platform for ultra-high paclitaxel-loaded multifunctional nanoparticles

S. Zhang, J. Zou, M. Elsabahy, A. Karwa, A. Li, D. A. Moore, R. B. Dorshow and K. L. Wooley, Chem. Sci., 2013, 4, 2122 DOI: 10.1039/C3SC50252J

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