Key Laboratory of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology), Ministry of Education, Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
Biomater Sci. 2021 Oct 26;9(21):7104-7114. doi: 10.1039/d1bm00185j.
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing technology is a promising approach for cancer therapy, and its application practice urgently requires a safe and effective gene carrier. In this work, we focus on the design of a phenylboronic acid (PBA)-functionalized, disulfide bonded branched polyaminoglycoside (SS-HPT-P) as a robust delivery vector of the CRISPR-Cas9 system. SS-HPT-P showed great tumor-targeting performance, reduction-responsive degradability, and gene transfection ability. The typical pCas9-surv (one CRISPR-Cas9 plasmid that targets and knocks out the survivin gene) delivery mediated by SS-HPT-P exhibited gene editing performance in the A549 cell line, confirming the feasibility of SS-HPT-P to effectively deliver the CRISPR-Cas9 system. SS-HPT-P/pCas9-surv could effectively inhibit the proliferation of tumor cells both and , suggesting the potential of PBA-functionalized nanocarriers for cancer gene therapy. The present work provides a promising approach for the treatment of malignant tumors.
簇状规律间隔短回文重复 (CRISPR)/CRISPR 相关蛋白 9 (Cas9) 基因编辑技术是癌症治疗的一种有前途的方法，其应用实践迫切需要安全有效的基因载体。在这项工作中，我们专注于设计一种苯硼酸 (PBA) 功能化、二硫键连接的支化聚氨基葡萄糖 (SS-HPT-P)，作为 CRISPR-Cas9 系统的强大递送载体。SS-HPT-P 表现出出色的肿瘤靶向性能、还原响应性降解能力和基因转染能力。由 SS-HPT-P 介导的典型 pCas9-surv（一种靶向并敲除生存素基因的 CRISPR-Cas9 质粒）传递在 A549 细胞系中表现出基因编辑性能，证实了 SS-HPT-P 有效传递 CRISPR-Cas9 系统的可行性。SS-HPT-P/pCas9-surv 可有效抑制肿瘤细胞的增殖，表明 PBA 功能化纳米载体在癌症基因治疗中的潜力。本工作为恶性肿瘤的治疗提供了一种有前途的方法。
