RNAi具有作为癌症治疗方法的显著潜力，但短干扰RNA（siRNA）有效且高效地传递到肿瘤仍然是一大难题。准确地制备功能性siRNA复合物、将足够剂量的siRNA定位到肿瘤细胞上并且使其内部化以及释放到细胞质中，仍然是个挑战。在这里，我们展示了一种复合物-包含siRNA，阳离子脂质和pH响应肽-适用于通过聚焦超声（FUS）增强肿瘤摄取。该复合物提供了有效的核酸封装、核酸酶保护和溶酶体逃逸，从而使细胞中的基因沉默明显比使用等效脂质体或商业试剂获得的效果更好。在携带MDA-MB-231乳腺癌异种移植体的小鼠中，使用近红外荧光标记的siRNA制备的脂质体和三元复合物脂质体：肽：siRNA复合物，在FUS治疗后在肿瘤中积累。因此，将设计良好的脂质体：肽：siRNA复合物与FUS肿瘤治疗相结合是实现体内基因传递强有力途径的有前途的方法。

RNAi has considerable potential as a cancer therapeutic approach, but effective and efficient delivery of short interfering RNA (siRNA) to tumors remains a major hurdle. It remains a challenge to prepare a functional siRNA complex, target enough dose to the tumor, and stimulate its internalization into tumor cells and its release to the cytoplasm. Here, we show how these key barriers to siRNA delivery can be overcome with a complex─comprising siRNA, cationic lipids, and pH-responsive peptides─that is suited to tumor uptake enhancement via focused ultrasound (FUS). The complex provides effective nucleic acid encapsulation, nuclease protection, and endosomal escape such that gene silencing in cells is substantially more effective than that obtained with either equivalent lipoplexes or commercial reagents. In mice bearing MDA-MB-231 breast cancer xenografts, both lipid and ternary, lipid:peptide:siRNA complexes, prepared with near-infrared fluorescently labeled siRNA, accumulate in tumors following FUS treatments. Therefore, combining a well-designed lipid:peptide:siRNA complex with FUS tumor treatments is a promising route to achieve robust in vivo gene delivery.