Despite evidence that microRNAs (miRNAs) are essential in modulating tumorigenesis, a major challenge in cancer treatment is to achieve tumor-specific selectivity and efficient yet safe delivery of miRNAs in vivo. In this study, we have developed a light-inducible silver nanoparticle nucleic acid delivery system that demonstrates precise spatiotemporal control, high cellular uptake, low cytotoxicity, escape from endosomes and release of functional miRNA into the cytosol. Using this approach, we delivered exogenous miR-148b to induce apoptosis in Ras-expressing keratinocytes and murine squamous cell carcinoma cells while avoiding cytotoxicity in untransformed keratinocytes. When administered to transgenic mice with HRas^G12V-driven skin tumors, a single dose of silver nanoparticle conjugates followed by 415 nm LED irradiation at the tumor site caused a rapid and sustained reduction in tumor volume by 92.8%, recruited T cells to the tumor site, and acted as a potent immunomodulator by polarizing the cytokine balance toward Th1 both locally and systemically. In summary, our results demonstrate that spatiotemporal controlled miR-148b mimic delivery can promote tumor regression efficiently and safely.

尽管有证据表明 microRNA (miRNA) 在调节肿瘤发生中是必不可少的，但癌症治疗的一个主要挑战是在体内实现肿瘤特异性选择性和有效而安全的 miRNA 递送。在这项研究中，我们开发了一种光诱导的银纳米粒子核酸递送系统，该系统展示了精确的时空控制、高细胞摄取、低细胞毒性、从内体逃逸以及将功能性 miRNA 释放到细胞质中。使用这种方法，我们提供外源 miR-148b 以诱导表达 Ras 的角质形成细胞和鼠鳞状细胞癌细胞凋亡，同时避免未转化角质形成细胞的细胞毒性。当给予具有 HRas ^{G12V 的}转基因小鼠时驱动的皮肤肿瘤，单剂量的银纳米粒子缀合物，然后在肿瘤部位进行 415 nm LED 照射，导致肿瘤体积快速持续减少 92.8%，将 T 细胞募集到肿瘤部位，并通过以下方式充当有效的免疫调节剂在局部和全身将细胞因子平衡向 Th1 极化。总之，我们的结果表明，时空控制的 miR-148b 模拟物递送可以有效且安全地促进肿瘤消退。