Zhang Shiyi, Zou Jiong, Elsabahy Mahmoud, Karwa Amolkumar, Li Ang, Moore Dennis A, Dorshow Richard B, Wooley Karen L
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.
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.
Chem Sci. 2013;4(5):2122-2126. doi: 10.1039/C3SC50252J.
A new type of degradable, nanoscopic polymer assembly containing ultra-high levels of drug loading covalent attachment within amphiphilic core-shell nanoparticle morphology has been generated as a potentially effective and safe anti-cancer agent. Poly(ethylene oxide)--polyphosphoester-based paclitaxel drug conjugates (PEO--PPE--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--PPE--PTX formed well-defined micelles in aqueous solution, with a PTX loading capacity as high as 65 %, 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--PPE--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.
一种新型的可降解纳米聚合物组装体已被制备出来，它具有两亲性核壳纳米颗粒形态，药物负载量超高且通过共价连接，有望成为一种有效且安全的抗癌药物。基于聚环氧乙烷-聚磷酸酯的紫杉醇药物偶联物（PEO-PPE-PTX）是通过快速、可扩展且通用的方法合成的，该方法仅涉及两个步骤：有机催化剂促进的开环聚合，然后是基于点击反应的紫杉醇前药偶联。聚合物与紫杉醇化学计量比的变化允许优化偶联效率、紫杉醇药物负载量以及整个聚合物和紫杉醇含量的所得水溶性。PEO-PPE-PTX在水溶液中形成明确的胶束，紫杉醇负载量高达65%，水中紫杉醇的最大浓度为6.2mg/mL，这比游离紫杉醇的水溶性高25000倍。证明了PEO-PPE-PTX对几种癌细胞系具有积极的细胞杀伤活性，并且侧链反应性功能的存在为未来涉及多种药物和成像剂偶联以实现化疗和生物成像的工作提供了一个强大的平台。
