Ultrasound-responsive microbubbles for sonography-guided siRNA delivery

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• 作者：Ping Wang ; MD^a ; ¹ ; Tinghui Yin ; MD^a ; ¹ ; Jingguo Li ; PhD^b ; Bowen Zheng ; MS^a ; Xiaoli Wang ; MS^a ; Yiru Wang ; PhD^b ; Jian Zheng ; MD^a ; Rongqin Zheng ; MD^a ; ^{zhengrq@mail.sysu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Xintao Shuai ; PhD^b ; ^c ; ^{shuaixt@mail.sysu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Microbubbles ; RNA interfering ; XIAP ; siRNA-loaded microbubble ; Contrast-enhanced ultrasound (CEUS)
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：12
• 期：4
• 页码：1139-1149
• 全文大小：2035 K

文摘

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. 1 MHz 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.