Shu Fangpeng, Lv Daojun, Song Xian-Lu, Huang Bin, Wang Chong, Yu Yuzhong, Zhao Shan-Chao
Department of Urology, Nanfang Hospital, Southern Medical University Guangzhou 510515 China
Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University Guangzhou 510095 China.
RSC Adv. 2018 Feb 9;8(12):6581-6589. doi: 10.1039/c7ra12969f. eCollection 2018 Feb 6.
Since metal organic frameworks (MOF) have exhibited fascinating potential in biomedical applications, it is worthwhile to construct a MOF-based multifunctional drug delivery system. In the present study, the anticancer drug doxorubicin (DOX) was loaded into zeolitic imidazolate framework-8 (ZIF-8) a one-pot process. The formed DOX@ZIF-8 was then coated with polydopamine, successively chelated with Fe and conjugated with hyaluronic acid (HA), finally resulting in a multifunctional ZIF-8 nanocarrier. The characterization results confirmed the successful formation of the hybrid nanocarrier. pH-responsive drug release of DOX was observed due to the innate pH-dependent stability of ZIF-8. Importantly, the flow cytometry and confocal laser scanning microscope results both verified the targeting ability of DOX@ZIF-HA toward prostate cancer PC-3 cells. The improved therapeutic efficacy of DOX@ZIF-HA when compared to the inhibited group was also demonstrated. Furthermore, the chelation of Fe by PDA makes the prepared DOX@ZIF-HA a good contrast agent for magnetic resonance (MR) imaging. Hence, we hope the constructed ZIF-8 based multifunctional nanocarrier could be a candidate for cancer theranostics.
由于金属有机框架(MOF)在生物医学应用中展现出了迷人的潜力,因此构建基于MOF的多功能药物递送系统是值得的。在本研究中,抗癌药物阿霉素(DOX)通过一锅法被载入沸石咪唑酯骨架-8(ZIF-8)中。然后将形成的DOX@ZIF-8用聚多巴胺包被,依次与铁螯合并与透明质酸(HA)偶联,最终得到一种多功能ZIF-8纳米载体。表征结果证实了杂化纳米载体的成功形成。由于ZIF-8固有的pH依赖性稳定性,观察到了DOX的pH响应性药物释放。重要的是,流式细胞术和共聚焦激光扫描显微镜结果均证实了DOX@ZIF-HA对前列腺癌PC-3细胞的靶向能力。与抑制组相比,DOX@ZIF-HA的治疗效果也得到了改善。此外,聚多巴胺对铁的螯合使得制备的DOX@ZIF-HA成为一种用于磁共振(MR)成像的良好造影剂。因此,我们希望构建的基于ZIF-8的多功能纳米载体能够成为癌症诊疗的候选者。