School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong 511442, P. R. China.
School of Medicine, South China University of Technology, Guangzhou 510006, PR China.
Biomater Sci. 2024 Apr 16;12(8):2057-2066. doi: 10.1039/d3bm02071a.
To date, five siRNA-based medications have received clinical approval and have demonstrated remarkable therapeutic efficacy in treating various diseases. However, their application has been predominantly limited to liver-specific diseases due to constraints in siRNA delivery capabilities. In this study, we have developed a siRNA delivery system utilizing clinically approved mPEG--PLGA, a cationic lipid, and an ionizable lipid. We optimized this system by carefully adjusting their mass ratios, resulting in highly efficient gene silencing. Furthermore, the optimized nanoparticle formulation, which encapsulates siRNA targeting CD47, induces a robust immune response. This response effectively suppresses the progression of melanoma tumors by blocking this critical immune checkpoint.
迄今为止，已有五种基于 siRNA 的药物获得临床批准，并在治疗各种疾病方面显示出显著的疗效。然而，由于 siRNA 递送能力的限制，它们的应用主要局限于肝脏特异性疾病。在本研究中，我们开发了一种利用临床批准的 mPEG--PLGA、阳离子脂质体和可离子化脂质的 siRNA 递送系统。我们通过仔细调整它们的质量比来优化该系统，从而实现高效的基因沉默。此外，优化后的纳米颗粒制剂可包裹靶向 CD47 的 siRNA，引发强烈的免疫反应。这种反应通过阻断这一关键免疫检查点有效地抑制了黑色素瘤肿瘤的进展。
