期刊
CHEMICAL SCIENCE
卷 4, 期 5, 页码 2122-2126出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c3sc50252j
关键词
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资金
- Covidien, Inc.
- National Heart Lung and Blood Institute of the National Institutes of Health [HHSN268201000046C]
- National Science Foundation [DMR-0906815, DMR-1105304]
- Welch Foundation through W. T. Doherty-Welch Chair in Chemistry [A-0001]
- NIH [P30 DC004665]
- NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS [P30DC004665] Funding Source: NIH RePORTER
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.
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