State Key Laboratory of Applied Organic Chemistry and Institute of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
Mol Pharm. 2013 May 6;10(5):1705-15. doi: 10.1021/mp300534a. Epub 2013 Apr 1.
Well-defined biocompatible magnetic and molecular dual-targeting polyelectrolyte hybrid hollow microspheres have been accomplished via the layer-by-layer (LbL) self-assembly technique. The hybrid shell was fabricated by the electrostatic interaction between the polyelectrolyte cation, chitosan (CS), and the hybrid anion, citrate modified ferroferric oxide nanoparticles (Fe3O4-CA), onto the uniform polystyrene sulfonate microsphere templates. Then the magnetic hybrid core/shell composite particles were modified with a linear, functional poly(ethylene glycol) (PEG) monoterminated with a biotargeting molecule (folic acid (FA)). Afterward the dual targeting hybrid hollow microspheres were obtained after etching the templates by dialysis. The dual targeting hybrid hollow microspheres exhibit exciting pH response and stability in high salt-concentration media. Their pH-dependent controlled release of the drug molecule (anticancer drug, doxorubicin (DOX)) was also investigated in different human body fluids. As expected, the cell viability of the HepG2 cells which decreased more rapidly was treated by the FA modified hybrid hollow microspheres rather than the unmodified one in the in vitro study. The dual-targeting hybrid hollow microspheres demonstrate selective killing of the tumor cells. The precise magnetic and molecular targeting properties and pH-dependent controlled release offers promise for cancer treatment.
通过层层自组装技术制备了具有良好生物相容性的磁性和分子双靶向聚电解质杂化中空微球。杂化壳通过聚电解质阳离子壳聚糖（CS）与杂化阴离子柠檬酸修饰的四氧化三铁纳米粒子（Fe3O4-CA）之间的静电相互作用在均匀的聚苯乙烯磺酸盐微球模板上形成。然后，将线性功能聚乙二醇（PEG）通过生物靶向分子（叶酸（FA））单端修饰磁性杂化核/壳复合粒子。然后通过透析刻蚀模板得到双靶向杂化中空微球。双靶向杂化中空微球在高盐浓度介质中表现出令人兴奋的 pH 响应和稳定性。还研究了它们在不同人体体液中的 pH 依赖性药物分子（抗癌药物阿霉素（DOX））的控制释放。如预期的那样，在体外研究中，用 FA 修饰的杂化中空微球处理的 HepG2 细胞的细胞活力下降更快，而未修饰的细胞活力下降更慢。双靶向杂化中空微球表现出对肿瘤细胞的选择性杀伤。精确的磁性和分子靶向特性以及 pH 依赖性控制释放为癌症治疗提供了希望。
