Shakeri-Zadeh Ali, Shiran Mohammad-Bagher, Khoee Sepideh, Sharifi Ali Mohammad, Ghaznavi Habib, Khoei Samideh
Medical Physics Department, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Polymer Chemistry Department, School of Sciences, University of Tehran, Tehran, Iran.
J Biomater Appl. 2014 Oct;29(4):548-56. doi: 10.1177/0885328214536940. Epub 2014 Jun 9.
The purpose of this study was to create an optimized method for preparation of 5-fluorouracil-loaded magnetic poly lactic-co-glycolic acid nanocapsules and to investigate its potential as multifunctional carriers to deliver therapeutic agents for tumor-targeted therapies. The in vitro release of the newly synthesized 5-fluorouracil-loaded poly lactic-co-glycolic acid magnetic nanocapsules was investigated in phosphate-buffered saline medium using the dialysis method. In vivo release studies of the magnetic nanocapsules were performed in rabbits. Finally, the targeting properties, anti-tumor, and pro-apoptotic effects of this new magnetic nanocapsule on CT26 cells allograft model were studied. The effective diameter of nanocapsules was 67.2 nm. In vivo release investigations showed that 5-fluorouracil has a sustained release profile, prolonged lifetime in the rabbit plasma, and increased tissue appetency when loaded into the magnetic nanocapsule. Magnetic resonance imaging confirmed that the magnetic nanocapsules were successfully targeted to the tumor. Additionally, the anti-tumor studies revealed that the targeted therapy with magnetic nanocapsules containing 5-fluorouracil effectively inhibits the growth of tumors compared with 5-fluorouracil alone (P < 0.01). The present study demonstrates that this new magnetic nanocapsule can be considered a new nanotechnology-based cancer chemotherapy agent in vivo.
本研究的目的是创建一种优化的方法来制备负载5-氟尿嘧啶的磁性聚乳酸-羟基乙酸共聚物纳米胶囊,并研究其作为多功能载体递送治疗剂用于肿瘤靶向治疗的潜力。采用透析法在磷酸盐缓冲盐溶液介质中研究了新合成的负载5-氟尿嘧啶的聚乳酸-羟基乙酸共聚物磁性纳米胶囊的体外释放。在兔子体内进行了磁性纳米胶囊的释放研究。最后,研究了这种新型磁性纳米胶囊对CT26细胞同种异体移植模型的靶向特性、抗肿瘤和促凋亡作用。纳米胶囊的有效直径为67.2nm。体内释放研究表明,5-氟尿嘧啶负载到磁性纳米胶囊中后具有缓释特性,在兔血浆中的寿命延长,组织亲和力增加。磁共振成像证实磁性纳米胶囊成功靶向肿瘤。此外,抗肿瘤研究表明,与单独使用5-氟尿嘧啶相比,含5-氟尿嘧啶的磁性纳米胶囊靶向治疗能有效抑制肿瘤生长(P<0.01)。本研究表明,这种新型磁性纳米胶囊可被视为一种基于纳米技术的新型体内癌症化疗药物。