Wei Chao-Gang, Zhang Rui, Wei Lan-Yi, Pan Peng, Zu He, Liu Ya-Zhen, Wang Yong, Shen Jun-Kang
Department of Radiology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, China.
Front Bioeng Biotechnol. 2022 Dec 14;10:1078342. doi: 10.3389/fbioe.2022.1078342. eCollection 2022.
Erythropoietin producing hepatocyte receptor A2 () is widely presented in the tumor cells, closely related to tumor cell migration, not cell apoptosis and proliferation. Based on its high expression in castration-resistant prostate cancer (CRPC), we herein develop a CRISPR-Cas9-based genome-editing nanomedicine to target erythropoietin producing hepatocyte receptor A2 for the treatment of castration-resistant prostate cancer. To this end, TAT was designed to stabilize the distribution of calcium, and then bound to ribonucleoprotein (RNP) to form nanoparticles RNP@CaP-TAT. This nanoparticle has a simple synthesis process with good biocompatible, to achieve the knockout of tumor cells (PC-3) targeting erythropoietin producing hepatocyte receptor A2 gene and to effectively suppress the migration of tumor cells. This delivery genome editing system provides a promising gene therapy strategy for the treatment of castration-resistant prostate cancer, showing good potential against castration-resistant prostate cancer tumor metastasis. In addition, it can be extended to other types of cancer with highly heterogeneous gene expression.
促红细胞生成素产生肝细胞受体A2（）广泛存在于肿瘤细胞中，与肿瘤细胞迁移密切相关，与细胞凋亡和增殖无关。基于其在去势抵抗性前列腺癌（CRPC）中的高表达，我们在此开发一种基于CRISPR-Cas9的基因组编辑纳米药物，以靶向促红细胞生成素产生肝细胞受体A2来治疗去势抵抗性前列腺癌。为此，设计TAT以稳定钙的分布，然后与核糖核蛋白（RNP）结合形成纳米颗粒RNP@CaP-TAT。这种纳米颗粒合成过程简单，具有良好的生物相容性，可实现对靶向促红细胞生成素产生肝细胞受体A2基因的肿瘤细胞（PC-3）的敲除，并有效抑制肿瘤细胞的迁移。这种递送基因组编辑系统为去势抵抗性前列腺癌的治疗提供了一种有前景的基因治疗策略，对去势抵抗性前列腺癌肿瘤转移显示出良好的潜力。此外，它可以扩展到其他具有高度异质性基因表达的癌症类型。
