Co-delivery of Sorafenib and CRISPR/Cas9 Based on Targeted Core–Shell Hollow Mesoporous Organosilica Nanoparticles for Synergistic HCC Therapy

• DOI: 10.1021/acsami.0c17660
• Publication Date: 2020-12-11T08:08:41Z
• Authors: Bing-Chen Zhang; Bang-Yue Luo; Jun-Jie Zou; Peng-Yu Wu; Jia-Li Jiang; Jing-Qing Le; Rui-Rui Zhao; Lu Chen; Jing-Wei Shao
• Keywords: Gene Editing; 0301 basic medicine; Drug Carriers; Carcinoma, Hepatocellular; Liver Neoplasms; Genes, erbB-1; Aptamers, Nucleotide; Epithelial Cell Adhesion Molecule; Silicon Dioxide; 3. Good health; ErbB Receptors; Drug Liberation; Mice; 03 medical and health sciences; CRISPR-Associated Protein 9; Cell Line, Tumor; Polyamines; Animals; Humans; Nanoparticles; CRISPR-Cas Systems; Porosity; Signal Transduction

The rapid development of CRISPR/Cas9 systems has opened up tantalizing prospects to sensitize cancers chemotherapy using efficient targeted genome editing, but safety concerns and possible off-target effects viral vectors remain a major obstacle for clinical application. Thus, the construction novel nonviral tumor-targeting nanodelivery great potential safe application gene–chemo-combination therapy. Here, we report polyamidoamine-aptamer-coated hollow mesoporous silica nanoparticle co-delivery sorafenib CRISPR/Cas9. core–shell nanoparticles had good stability, enabled ultrahigh drug loading, delivery, controlled-release gene–drug combination. nanocomplex showed >60% EGFR-editing efficiency without in all nine similar sites, regulating EGFR-PI3K-Akt pathway inhibit angiogenesis, exhibited synergistic effect on cell proliferation. Importantly, nanosystem achieved EGFR gene therapy caused 85% tumor inhibition mouse model. Furthermore, high accumulation at site vivo with no damage organs. Due these properties, provides versatile delivery approach co-loading combinations, allowing precise editing growth apparent side normal tissues.