Magnetic Nanocarriers of Doxorubicin Coated with Poly(ethylene glycol) and Folic Acid: Relation between Coating Structure, Surface Properties, Colloidal Stability, and Cancer Cell Targeting
Magnetic Nanocarriers of Doxorubicin Coated with Poly(ethylene glycol) and Folic Acid: Relation between Coating Structure, Surface Properties, Colloidal Stability, and Cancer Cell Targeting
复制标题
DOI：
10.1021/la2037845
复制
发表时间：
2012-01-17
期刊：
影响因子：
3.9
通讯作者：
Chourpa, Igor
中科院分区：
文献类型：
--
作者：
Kaaki, Karine;Herve-Aubert, Katel;Chourpa, Igor
我们报告了可用于癌症治疗和诊断（治疗诊断）的新型生物相容性纳米系统的有效一步合成和详细的物理化学评估。这些系统是超顺磁性氧化铁纳米粒子（SPION），其携带抗癌药物阿霉素并涂有共价键合的生物相容性聚合物聚乙二醇（PEG），其是天然的并用生物癌症靶向配体叶酸（PEG-FA）进行修饰。这些多功能纳米粒子（SPION-DOX-PEG-FA）旨在合理结合癌细胞靶向（磁性和生物）、双模癌细胞成像（通过MRI和荧光）和双模癌症治疗（通过靶向药物输送和热疗效应）的多级机制。然而，为了使这些概念协同工作，成分和颗粒结构的选择至关重要。因此，在目前的工作中，通过几种表面特定的仪器方法对杂化纳米颗粒的有机涂层进行了详细的物理化学表征，包括表面增强拉曼散射（SERS）光谱、X射线光电子能谱（XPS）和飞行时间二次离子质谱（ToF-SIMS）。我们证明抗癌药物阿霉素附着在氧化铁表面并埋在聚合物层下，而叶酸位于有机涂层的最表面。有趣的是，颗粒表面适度存在叶酸不会增加颗粒表面电位，但足以增加 MCF-7 癌细胞对颗粒的摄取。所有这些原始结果都有助于更好地理解混合生物相容性纳米系统的结构活性关系，并鼓励其在癌症治疗诊断中的应用。
We report the efficient one-step synthesis and detailed physicochemical evaluation of novel biocompatible nanosystems useful for cancer therapeutics and diagnostics (theranostics). These systems are the superparamagnetic iron oxide nanoparticles (SPIONs) carrying the anticancer drug doxorubicin and coated with the covalently bonded biocompatible polymer poly(ethylene glycol) (PEG), native and modified with the biological cancer targeting ligand folic acid (PEG-FA). These multifunctional nanoparticles (SPION-DOX-PEG-FA) are designed to rationally combine multilevel mechanisms of cancer cell targeting (magnetic and biological), bimodal cancer cell imaging (by means of MRI and fluorescence), and bimodal cancer treatment (by targeted drug delivery and by hyperthermia effect). Nevertheless, for these concepts to work together, the choice of ingredients and particle structure are critically important. Therefore, in the present work, a detailed physicochemical characterization of the organic coating of the hybrid nanoparticles is performed by several surface-specific instrumental methods, including surface-enhanced Raman scattering (SERS) spectroscopy, X-ray photoelectron spectrometry (XPS), and time-of-flight secondary ion mass spectrometry (ToF-SIMS). We demonstrate that the anticancer drug doxorubicin is attached to the iron oxide surface and buried under the polymer layers, while folic acid is located on the extreme surface of the organic coating. Interestingly, the moderate presence of folic acid on the particle surface does not increase the particle surface potential, while it is sufficient to increase the particle uptake by MCF-7 cancer cells. All of these original results contribute to the better understanding of the structure activity relationship for hybrid biocompatible nanosystems and are encouraging for the applications in cancer theranostics.