NanoScience Technology Center, College of Medicine, Chemistry Department, University of Central Florida, Orlando, Florida 32826, United States.
Biomacromolecules. 2011 Nov 14;12(11):3917-27. doi: 10.1021/bm2009334. Epub 2011 Sep 30.
The development of functional amino acid-based polymeric materials is emerging as a platform to create biodegradable and nontoxic nanomaterials for medical and biotechnology applications. In particular, facile synthetic routes for these polymers and their corresponding polymeric nanomaterials would have a positive impact in the development of novel biomaterials and nanoparticles. However, progress has been hampered by the need to use complex protection-deprotection methods and toxic phase transfer catalysts. In this study, we report a facile, single-step approach for the synthesis of an N-alkylated amino acid as an AB-type functional monomer to generate a novel pseudo-poly(amino acid), without using the laborious multistep, protection-deprotection methods. This synthetic strategy is reproducible, easy to scale up, and does not produce toxic byproducts. In addition, the synthesized amino acid-based polymer is different from conventional linear polymers as the butyl pendants enhance its solubility in common organic solvents and facilitate the creation of hydrophobic nanocavities for the effective encapsulation of hydrophobic cargos upon nanoparticle formation. Within the nanoparticles, we have encapsulated a hydrophobic DiI dye and a therapeutic drug, Taxol. In addition, we have conjugated folic acid as a folate receptor-targeting ligand for the targeted delivery of the nanoparticles to cancer cells expressing the folate receptor. Cell cytotoxicity studies confirm the low toxicity of the polymeric nanoparticles, and drug-release experiments with the Taxol-encapsulated nanoparticles only exhibit cytotoxicity upon internalization into cancer cells expressing the folate receptor. Taken together, these results suggested that our synthetic strategy can be useful for the one-step synthesis of amino acid-based small molecules, biopolymers, and theranostic polymeric nanoagents for the targeted detection and treatment of cancer.
基于功能氨基酸的聚合物材料的发展正在成为一种平台，用于为医学和生物技术应用创造可生物降解和无毒的纳米材料。特别是，这些聚合物及其相应的聚合物纳米材料的简便合成途径将对新型生物材料和纳米颗粒的发展产生积极影响。然而，由于需要使用复杂的保护-脱保护方法和有毒的相转移催化剂，进展受到了阻碍。在这项研究中，我们报告了一种简便的、一步法合成 N-烷基化氨基酸作为 AB 型功能单体的方法，用于生成一种新型的假聚（氨基酸），而无需使用繁琐的多步保护-脱保护方法。这种合成策略具有可重复性、易于放大且不产生有毒副产物。此外，合成的氨基酸基聚合物与常规线性聚合物不同，因为丁基侧链增强了其在常见有机溶剂中的溶解性，并有利于形成疏水性纳米腔，以便在形成纳米颗粒时有效封装疏水性载药。在纳米颗粒内，我们封装了疏水性 DiI 染料和治疗药物紫杉醇。此外，我们还缀合了叶酸作为叶酸受体靶向配体，用于将纳米颗粒靶向递送到表达叶酸受体的癌细胞。细胞毒性研究证实了聚合物纳米颗粒的低毒性，并且包封紫杉醇的纳米颗粒的药物释放实验仅在表达叶酸受体的癌细胞内化后才表现出细胞毒性。总之，这些结果表明，我们的合成策略可用于一步法合成基于氨基酸的小分子、生物聚合物和治疗性聚合物纳米制剂，用于癌症的靶向检测和治疗。
