Rauf Mohd Ahmar, Rao Afifa, Sivasoorian Siva Sankari, Iyer Arun K
Department of Internal Medicine, Heme/Oncology Unit, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA.
Cells. 2025 Jul 23;14(15):1136. doi: 10.3390/cells14151136.
CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats-associated protein 9)-mediated genome editing has emerged as a transformative tool in medicine, offering significant potential for cancer therapy because of its capacity to precisely target and alter the genetic modifications associated with the disease. However, a major challenge for its clinical translation is the safe and efficient in vivo delivery of CRISPR/Cas9 components to target cells. Nanotechnology is a promising solution to this problem. Nanocarriers, owing to their tunable physicochemical properties, can encapsulate and protect CRISPR/Cas9 components, enabling targeted delivery and enhanced cellular uptake. This review provides a comprehensive examination of the synergistic potential of CRISPR/Cas9 and nanotechnology in cancer therapy and explores their integrated therapeutic applications in gene editing and immunotherapy. A critical aspect of in vivo CRISPR/Cas9 application is to achieve effective localization at the tumor site while minimizing off-target effects. Nanocarriers can be engineered to overcome biological barriers, thereby augmenting tumor-specific delivery and facilitating intracellular uptake. Furthermore, their design allows for controlled release of the therapeutic payload, ensuring sustained efficacy and reduced systemic toxicity. The optimization of nanocarrier attributes, including size, shape, surface charge, and composition, is crucial for improving the cellular internalization, endosomal escape, and nuclear localization of CRISPR/Cas9. Moreover, surface functionalization with targeting ligands can enhance the specificity of cancer cells, leading to improved gene-editing accuracy. This review thoroughly discusses the challenges associated with in vivo CRISPR/Cas9 delivery and the innovative nanotechnological strategies employed to overcome them, highlighting their combined potential for advancing cancer treatment for clinical application.
CRISPR/Cas9（成簇规律间隔短回文重复序列相关蛋白9）介导的基因组编辑已成为医学领域的一种变革性工具，因其能够精确靶向并改变与疾病相关的基因修饰，在癌症治疗方面具有巨大潜力。然而，其临床转化面临的一个主要挑战是如何将CRISPR/Cas9组件安全有效地递送至体内靶细胞。纳米技术是解决这一问题的一个有前景的方案。纳米载体因其可调节的物理化学性质，能够包裹并保护CRISPR/Cas9组件，实现靶向递送并增强细胞摄取。本文综述全面审视了CRISPR/Cas9与纳米技术在癌症治疗中的协同潜力，并探讨了它们在基因编辑和免疫治疗中的综合治疗应用。体内应用CRISPR/Cas9的一个关键方面是在将脱靶效应降至最低的同时，实现其在肿瘤部位的有效定位。可以对纳米载体进行工程设计以克服生物屏障，从而增强肿瘤特异性递送并促进细胞内摄取。此外，其设计允许治疗性载荷的控释，确保疗效持续并降低全身毒性。优化纳米载体的属性，包括尺寸、形状、表面电荷和组成，对于提高CRISPR/Cas9的细胞内化、内体逃逸和核定位至关重要。此外，用靶向配体进行表面功能化可以增强对癌细胞的特异性，从而提高基因编辑的准确性。本文综述深入讨论了体内递送CRISPR/Cas9相关的挑战以及为克服这些挑战而采用的创新性纳米技术策略，突出了它们在推进癌症治疗临床应用方面的综合潜力。
