title: 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 loadingviacovalent 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 65wt%, 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.
authors.affiliation: Departments of Chemistry and Chemical Engineering, Laboratory for Synthetic-Biologic Interactions, Texas A&M University, P.O. BOX 30012, 3255 TAMU, College Station, TX 77842, USA ; Department of Chemistry, Washington University in St. Louis, St. Louis, MO 63130, USA.
authors.forename: Shiyi
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Departments of Chemistry and Chemical Engineering, Laboratory for Synthetic-Biologic Interactions, Texas A&M University, P.O. BOX 30012, 3255 TAMU, College Station, TX 77842, USA.
authors.forename: Jiong
authors.initials: J
authors.lastname: Zou
authors.affiliation: Departments of Chemistry and Chemical Engineering, Laboratory for Synthetic-Biologic Interactions, Texas A&M University, P.O. BOX 30012, 3255 TAMU, College Station, TX 77842, USA ; Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Elsabahy
authors.affiliation: Covidien Pharmaceuticals R&D, Hazelwood, MO 63042, USA.
authors.forename: Amolkumar
authors.initials: A
authors.lastname: Karwa
authors.affiliation: Departments of Chemistry and Chemical Engineering, Laboratory for Synthetic-Biologic Interactions, Texas A&M University, P.O. BOX 30012, 3255 TAMU, College Station, TX 77842, USA ; Al-Deera Holding USA, Inc., New York, NY 10019.
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.affiliation: Covidien Pharmaceuticals R&D, Hazelwood, MO 63042, USA.
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Moore
authors.affiliation: Covidien Pharmaceuticals R&D, Hazelwood, MO 63042, USA ; MediBeacon, Inc., St. Louis, MO 63146, USA.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Dorshow
authors.affiliation: Departments of Chemistry and Chemical Engineering, Laboratory for Synthetic-Biologic Interactions, Texas A&M University, P.O. BOX 30012, 3255 TAMU, College Station, TX 77842, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Wooley