Poly(ethylene oxide)-block-polyphosphester-based Paclitaxel Conjugates as a Platform for Ultra-high Paclitaxel-loaded Multifunctional Nanoparticles.
Poly(ethylene oxide)-block-polyphosphester-based Paclitaxel Conjugates as a Platform for Ultra-high Paclitaxel-loaded Multifunctional Nanoparticles.
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DOI：
10.1039/c3sc50252j
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发表时间：
2013
期刊：
影响因子：
8.4
通讯作者：
Wooley KL
中科院分区：
文献类型：
--
作者：
Zhang S;Zou J;Elsabahy M;Karwa A;Li A;Moore DA;Dorshow RB;Wooley KL
一种新型的可降解的纳米级聚合物组件通过两亲性核-壳纳米颗粒形态的共价附着，含有超高水平的药物负载，已经成为一种潜在的有效和安全的抗癌药物。聚（环氧乙烷）-嵌段聚磷酸酯基紫杉醇药物偶联物（PEO-b-PPE-g-PTX）是一种快速、可扩展和通用的方法，只涉及两个步骤：有机催化剂促进的开环聚合，然后是PTX前药的基于点击反应的偶联。聚合物-PTX化学计量的变化可以优化偶联效率、PTX载药量、整个聚合物的水溶性和PTX含量。PEO-b-PPE-g-PTX在水溶液中形成了明确的胶束，PTX负载量高达65 wt%， PTX在水中的最大浓度为6.2 mg/mL，比游离PTX的水溶解度高25000倍。PEO-b-PPE-g-PTX对几种癌细胞系的阳性细胞杀伤活性已被证实，其悬垂反应功能的存在为未来涉及多种药物和显像剂的偶联以实现化疗和生物成像的工作提供了强大的平台。
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.