Department of Gynecology, The Second Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, China; Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, China.
Department of Gynecology, The Second Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, China.
Cancer Lett. 2015 Sep 1;365(2):156-65. doi: 10.1016/j.canlet.2015.05.003. Epub 2015 Jun 6.
Recent advances in efficient microRNA (miRNA) delivery techniques using prostate cancer-targeted nanoparticles offer critical information for understanding the functional role of miRNAs in vivo, and for supporting targeted gene therapy in terms of treating miRNA-associated prostate cancer. Here, we report the polyarginine peptide (R11)-labeled non-toxic SSPEI nanomaterials capable of prostate cancer-specific miR-145 delivery to prostate cancer in vivo where they display full bioactivity at completely nontoxic concentrations. The R11-labeled BPEI-SS (R11-SSPEI) nanocarrier showed less toxicity in prostate cancer, and electrostatic interaction of R11-SSPEI with miR-145 exhibited optimal transfection efficacy. The R11-SSPEI/miR-145 polymer could be specifically uptaken in prostate cancer using FAM-miR-145 mixed with R11-SSPEI. The functional action of miR-145 oligomers released from polyplexes was evaluated by a reporter vector containing a miR-145-binding sequence, and showed a significantly reduced reporter signal in a dose-dependent manner. More importantly, in a peritoneal mouse tumor model, the systemic administration of the R11-SSPEI/FAM-miR-145 complex leads to the delivery of miR-145 into the tumors, dramatically inhibiting tumor growth and prolonged survival time. Hence, we establish a novel and prostate cancer-specific targeting system for the systemic in vivo application of microRNAs through R11-SSPEI complexation as a powerful tool for future therapeutic use.
最近在使用前列腺癌靶向纳米颗粒的高效 microRNA（miRNA）传递技术方面取得了进展，为了解 miRNA 在体内的功能作用以及支持针对 miRNA 相关前列腺癌的靶向基因治疗提供了关键信息。在这里，我们报告了聚精氨酸肽（R11）标记的无毒 SSPEI 纳米材料，能够在体内将特异性的 miR-145 递送至前列腺癌，并且在完全无毒浓度下显示出完全的生物活性。R11 标记的 BPEI-SS（R11-SSPEI）纳米载体在前列腺癌中的毒性较低，并且 R11-SSPEI 与 miR-145 的静电相互作用表现出最佳的转染效果。使用 FAM-miR-145 混合 R11-SSPEI 可以特异性地摄取前列腺癌细胞中的 R11-SSPEI/miR-145 聚合物。通过含有 miR-145 结合序列的报告载体评估从多聚物中释放的 miR-145 寡聚物的功能作用，结果显示报告信号呈剂量依赖性显著降低。更重要的是，在腹膜小鼠肿瘤模型中，全身性给予 R11-SSPEI/FAM-miR-145 复合物可将 miR-145 递送至肿瘤中，显著抑制肿瘤生长并延长生存时间。因此，我们通过 R11-SSPEI 复合物建立了一种新型的前列腺癌特异性靶向系统，可用于 miRNA 的系统体内应用，作为未来治疗用途的有力工具。
