Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, and Institute of Pharmacy & Pharmacology, School of Pharmaceutical Science, University of South China, Hengyang 421001, China; Hunan Province Key Laboratory for Antibody-Based Drug and Intelligent Delivery System, School of Pharmaceutical Sciences, Hunan University of Medicine, Huaihua 418000, China.
Hunan Province Key Laboratory for Antibody-Based Drug and Intelligent Delivery System, School of Pharmaceutical Sciences, Hunan University of Medicine, Huaihua 418000, China; College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China.
Colloids Surf B Biointerfaces. 2022 Feb;210:112257. doi: 10.1016/j.colsurfb.2021.112257. Epub 2021 Dec 1.
The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) systems have emerged as robust tools in cancer gene therapy due to their simplicity and versatility. Nevertheless, the genome editing efficiency in tumor sites and the clinical applications of CRISPR/Cas have been compromised by non-specific delivery and genotoxicity. Recently, intelligent delivery systems incorporating sensitive materials in response to endogenous stimuli of the tumor microenvironment (TME) have represented viable platforms for tumor-specific genome editing and reduced side effects of CRISPR/Cas. Spurred by this promising direction, this review first introduces the CRISPR/Cas systems widely employed in cancer therapeutic explorations. Various types of CRISPR/Cas delivery systems sensitive to the stimuli in TME and typical dual-/multiple-responsive CRISPR/Cas carriers are further discussed, emphasizing the correlations between sensitive components and spatiotemporal delivery mechanisms. The genome editing efficiencies of CRISPR/Cas-loaded stimuli-responsive carriers are also summarized both in vitro and in vivo. Collectively, stimuli-responsive CRISPR/Cas delivery systems hold great promise for potent cancer gene therapy.
成簇规律间隔短回文重复序列（CRISPR）/CRISPR 相关蛋白（Cas）系统因其简单性和多功能性已成为癌症基因治疗中的强大工具。然而，由于非特异性递送和遗传毒性，肿瘤部位的基因组编辑效率和 CRISPR/Cas 的临床应用受到了影响。最近，将对肿瘤微环境（TME）内源性刺激作出响应的敏感材料纳入其中的智能递药系统已成为肿瘤特异性基因组编辑和降低 CRISPR/Cas 副作用的可行平台。受这一有前景的方向的推动，本综述首先介绍了广泛应用于癌症治疗探索的 CRISPR/Cas 系统。进一步讨论了对 TME 中的刺激敏感的各种类型的 CRISPR/Cas 递药系统和典型的双重/多重响应性 CRISPR/Cas 载体，强调了敏感成分与时空递药机制之间的相关性。还总结了 CRISPR/Cas 负载的刺激响应性载体在体外和体内的基因组编辑效率。总之，对刺激敏感的 CRISPR/Cas 递药系统为有效的癌症基因治疗带来了巨大的希望。
