School of Engineering, Indian Institute of Technology Mandi, Himachal Pradesh, India.
School of Basic Sciences, Indian Institute of Technology Mandi, Himachal Pradesh, India.
Sci Rep. 2017 Oct 3;7(1):12598. doi: 10.1038/s41598-017-12786-6.
Metal organic frameworks (MOFs) exhibit unique features of finely tunable pore structures, excellent chemical stability and flexible surface structural functionality, making them advantageous for a wide range of applications including energy storage, compound separation, catalysis, and drug delivery. The present work enlightens a novel approach of single step fabrication of CCM-ZIF-8 as a drug carrier and its application as stimuli responsive drug delivery systems via external stimuli involving change in pH and in presence of biomimetic cell membrane like environment using liposomes and SDS micelles. The methodology is devoid of any post synthesis drug loading steps. The synthesized curcumin encapsulated ZIF-8 frameworks demonstrate ultrahigh drug encapsulation efficiency (ca. 83.33%) and good chemical stability. In vitro drug release of curcumin was three times higher in acidic medium than in physiological pH. Cytotoxicity results demonstrated enhanced therapeutic effect of CCM-ZIF-8 than free curcumin. Confocal microscopy results confirmed the easy cellular internalization of CCM-ZIF-8 in HeLa cells. Intracellular distribution studies at various incubation times confirmed the clathrin-mediated endocytosis to lysosomal pathway of CCM-ZIF-8, but without mitochondria being an intracellular fate. The results signify that CCM-ZIF-8 is an efficient drug carrier for passive tumor therapy in future for cancer treatments.
金属有机骨架(MOFs)具有精细可调的孔结构、优异的化学稳定性和灵活的表面结构功能等独特特点,使其在储能、化合物分离、催化和药物输送等广泛应用中具有优势。本工作提出了一种新颖的一步法制备 CCM-ZIF-8 作为药物载体的方法,并通过外部刺激(涉及 pH 变化和仿生细胞膜环境存在时使用脂质体和 SDS 胶束)将其应用于刺激响应型药物输送系统。该方法不涉及任何合成后药物负载步骤。合成的姜黄素包封 ZIF-8 框架表现出超高的药物包封效率(约 83.33%)和良好的化学稳定性。在酸性介质中的姜黄素体外释放是生理 pH 下的三倍。细胞毒性结果表明 CCM-ZIF-8 的治疗效果优于游离姜黄素。共聚焦显微镜结果证实 CCM-ZIF-8 易于在 HeLa 细胞中被细胞内化。不同孵育时间的细胞内分布研究证实 CCM-ZIF-8 是通过网格蛋白介导的内吞作用进入溶酶体途径,但线粒体不是其细胞内命运。这些结果表明,CCM-ZIF-8 是未来癌症治疗中被动肿瘤治疗的有效药物载体。