School of Chemistry, College of Science , University of Tehran , Tehran 14155-6455 , Iran.
Monoclonal Antibody Research Center, Avicenna Research Institute , ACECR , Tehran 19615-1177 , Iran.
ACS Appl Mater Interfaces. 2018 May 30;10(21):17594-17604. doi: 10.1021/acsami.8b03111. Epub 2018 May 17.
Designable coordination polymers with suitable chemical diversities and biocompatible structures have been proposed as a promising class of vehicles for drug delivery systems. Here, we hydrothermally synthesized a novel one-dimensional (1D) coordination polymer, Zn(HO)K(HBTC)(HO)·2HO, where HBTC = benzene-1,3,5-tricarboxylic acid (trimesic acid), cp.1. As the hydrogen bonds stabilized 1D chains in three dimensions, the cp.1 could be a good candidate for delivering small-molecule chemotherapeutics such as 5-fluorouracil (5-Fu). The synthesized cp.1 showed a remarkable 5-Fu loading of 66% with encapsulation efficiency of 98% and almost complete release process. The 5-Fu-loaded cp.1 displayed a time-dependent cytotoxicity effect against breast cancer cell lines MCF-7 and 4T1. The cellular uptake of cp.1 particles was investigated via confocal laser scanning microscopy using fluorescein isothiocyanate and LysoTracker Red staining. Furthermore, the in vivo antitumor impact of 5-Fu-loaded cp.1 was studied on 4T1 breast cancer BALB/c mice model. The intratumor treatment of 5-Fu-loaded cp.1 demonstrated beneficial antitumor efficacy by postponing tumor growth. These results suggest that the 5-Fu-loaded cp.1 microparticles with a great locoregional delivery can be efficient anticancer drug carriers for further clinical treatments.
具有合适化学多样性和生物相容性结构的设计协调聚合物已被提议作为药物传递系统的一类有前途的载体。在这里,我们水热合成了一种新型的一维(1D)配位聚合物,[Zn(HO)K(HBTC)(HO)](HBTC)·2HO,其中 HBTC = 苯-1,3,5-三羧酸(均苯三甲酸),cp.1。由于氢键稳定了三维中的 1D 链,cp.1 可能是输送小分子化疗药物(如 5-氟尿嘧啶(5-Fu))的良好候选物。合成的 cp.1 表现出出色的 5-Fu 负载能力,负载量为 66%,封装效率为 98%,几乎完全释放过程。负载 5-Fu 的 cp.1 对乳腺癌细胞系 MCF-7 和 4T1 表现出时间依赖性细胞毒性作用。通过使用荧光素异硫氰酸酯和 LysoTracker Red 染色的共聚焦激光扫描显微镜研究了 cp.1 颗粒的细胞摄取。此外,还研究了负载 5-Fu 的 cp.1 在 4T1 乳腺癌 BALB/c 小鼠模型中的体内抗肿瘤作用。负载 5-Fu 的 cp.1 的肿瘤内治疗通过延迟肿瘤生长,展示了有益的抗肿瘤功效。这些结果表明,负载 5-Fu 的 cp.1 微颗粒具有良好的局部递药能力,可以作为进一步临床治疗的高效抗癌药物载体。