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-b-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.

中文翻译：

---

用于 siRNA 递送和癌症免疫治疗的脂质辅助聚合物纳米粒子的优化

迄今为止，已有五种基于siRNA的药物已获得临床批准，并在治疗多种疾病方面表现出显着的疗效。然而，由于 siRNA 递送能力的限制，它们的应用主要限于肝脏特异性疾病。在这项研究中，我们利用临床批准的 mPEG -b -PLGA、阳离子脂质和可电离脂质开发了 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，优化的纳米颗粒制剂封装了靶向 CD47 的 siRNA，可诱导强大的免疫反应。这种反应通过阻断这一关键的免疫检查点，有效抑制黑色素瘤的进展。