Bioinspired metal–organic frameworks mediated efficient delivery of siRNA for cancer therapy

Abstract Small interfering RNA (siRNA) has emerged as a powerful tool in gene therapy to suppress gene expression. However, the fragile properties of siRNA and the low efficiency with non-specific gene delivery systems compromised the therapeutic effect of siRNA. Metal-organic frameworks (MOFs) are hybrid materials constructed by organic bridging ligands and metal cations with extremely high binding affinity with nuclei acids. But the properties of MOF-based nanoparticles, such as short circulation lifetime or non-specificity, hindered its application for cancer therapy. Herein, we fabricated a cancer cell membrane camouflaged zeolitic imidazolate framework 8 (ZIF-8)-based metal–organic frameworks (CAMEL) nanoparticles for targeted delivery of siRNA to knockdown Plk1 gene in tumors. ZIF-8 had high loading efficiency of siRNA, and the MOF-based nucleic acids complexes could be prepared at an adult dose once conveniently, which was not reported yet. MOF facilitated the release of siRNA from lysosomes. Cell membrane coating achieves targeted delivery of siRNA to tumor tissue and subsequent PLK1 silencing for tumor suppression. Our work developed a novel MOF-based nucleic acid delivery system for precise cancer therapy.