Department of Medical Ultrasonic, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
PCFM Lab of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, China.
Nanomedicine. 2016 May;12(4):1139-1149. doi: 10.1016/j.nano.2015.12.361. Epub 2015 Dec 28.
RNA interfering is a gene therapeutic approach of great potential for cancer. However, tumor-targeted delivery of small interfering RNA (siRNA) solely based on the enhanced permeability and retention effect of nanocarriers is often insufficient. To address this challenge, siRNA encapsulated ultrasound-responsive microbubble (MB) was developed from polymeric siRNA micelles and liposomal MBs using hetero-assembling strategy. 1MHz low-frequency ultrasound exposure of the tumor site after intratumoral injection of XIAP siRNA/MBs led to enhanced permeability for much more siRNA delivery into deep tumor regions. Significant improvement of XIAP gene silencing and cleaved caspase-3 activation was achieved, resulting in good therapeutic effect on human cervical cancer xenograft model in nude mice. Moreover, real-time US monitoring of the tumor was also possible using the siRNA/MBs as a contrast agent during the therapeutic process. These results show that the multi-functional siRNA/MBs are a promising theranostic system for cancer gene therapy.
RNA 干扰是一种极具潜力的癌症基因治疗方法。然而，单纯基于纳米载体的增强通透性和滞留效应将小干扰 RNA（siRNA）靶向递送至肿瘤部位往往是不够的。为了解决这一挑战，我们采用杂化组装策略，从聚合物 siRNA 胶束和脂质体 MB 中开发出了超声响应性微泡（MB）包封的 siRNA。在肿瘤内注射 XIAP siRNA/MB 后，对肿瘤部位进行 1MHz 低频超声辐照，可增强通透性，使更多的 siRNA 递送至深部肿瘤区域。这显著提高了 XIAP 基因沉默和裂解 caspase-3 的激活水平，从而在裸鼠人宫颈癌异种移植模型中取得了良好的治疗效果。此外，还可以使用 siRNA/MB 作为治疗过程中的造影剂，实时进行肿瘤的超声监测。这些结果表明，多功能 siRNA/MB 是一种很有前途的癌症基因治疗的治疗诊断系统。
