Department of Chemistry, Payame Noor University, P.O. BOX: 19395-3697, Tehran, Iran.
Department of Polymer, Faculty of Engineering, University of Bonab, P.O. Box: 55517, Bonab, Iran.
Int J Biol Macromol. 2018 Oct 15;118(Pt B):1871-1879. doi: 10.1016/j.ijbiomac.2018.07.036. Epub 2018 Jul 12.
The aim of this study was the design and development of a novel de novo drug delivery system for cancer chemotherapy. For this purpose, chitosan (CS) functionalized using phthalic anhydride followed by 4-cyano, 4-[(phenylcarbothioyl) sulfanyl] pentanoic acid as a chain transfer agent (CTA) to afford CS-CTA macroinitiator. The synthesized CS-CTA macroinitiator was then copolymerized with methacrylic acid (MAA) monomer using reversible addition-fragmentation chain transfer (RAFT) polymerization technique to produce chitosan-graft-poly(methacrylic acid) (CS-g-PMAA) graft copolymer. Afterward, graphene oxide (GO) nanosheets were incorporated into the synthesized copolymer through the physical interactions. The CS-g-PMAA/GO nanocomposite was loaded with doxorubicin hydrochloride (DOX) as a universal anticancer drug. The biocompatibility, DOX-loading capacity, and pH dependent drug release behavior of the developed nanocomposite were also investigated. As the experimental results, as well as superior biological and physicochemical features of CS and GO, we envision that the developed CS-g-PMAA/GO nanocomposite may be applied as de novo drug delivery nanosystem for cancer chemotherapy.
本研究旨在设计和开发一种新型的癌症化疗从头药物输送系统。为此，使用邻苯二甲酸酐对壳聚糖（CS）进行功能化，然后使用 4-氰基、4-[(苯甲酰硫基)磺酰基]戊酸作为链转移剂（CTA），以提供 CS-CTA 大分子引发剂。然后，使用可逆加成-断裂链转移（RAFT）聚合技术将合成的 CS-CTA 大分子引发剂与甲基丙烯酸（MAA）单体共聚，以制备壳聚糖接枝聚（甲基丙烯酸）（CS-g-PMAA）接枝共聚物。之后，通过物理相互作用将氧化石墨烯（GO）纳米片掺入合成的共聚物中。将盐酸多柔比星（DOX）负载到合成的 CS-g-PMAA/GO 纳米复合材料中作为通用抗癌药物。还研究了开发的纳米复合材料的生物相容性、DOX 载药量和 pH 值依赖性药物释放行为。正如实验结果以及 CS 和 GO 的优异的生物和物理化学特性所示，我们设想开发的 CS-g-PMAA/GO 纳米复合材料可作为癌症化疗的从头药物输送纳米系统。
