title: Ultrasound-responsive microbubbles for sonography-guided siRNA delivery.
abstract: 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.
authors.affiliation: Department of Medical Ultrasonic, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Medical Ultrasonic, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Tinghui
authors.initials: T
authors.lastname: Yin
authors.affiliation: PCFM Lab of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jingguo
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Medical Ultrasonic, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Zheng
authors.affiliation: Department of Medical Ultrasonic, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.affiliation: PCFM Lab of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yiru
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medical Ultrasonic, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Medical Ultrasonic, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. Electronic address: zhengrq@mail.sysu.edu.cn.
authors.forename: Rongqin
authors.initials: R
authors.lastname: Zheng
authors.affiliation: PCFM Lab of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, China; Center of Biomedical Engineering, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. Electronic address: shuaixt@mail.sysu.edu.cn.
authors.forename: Xintao
authors.initials: X
authors.lastname: Shuai
mesh_terms: D000818:Animals; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage; D051379:Mice; D008823:Micelles; D045423:Microbubbles / Q000627:therapeutic use; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D010539:Permeability / Q000187:drug effects; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014463:Ultrasonography; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D008081:Liposomes; D008823:Micelles; D034741:RNA, Small Interfering; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human
keywords: Contrast-enhanced ultrasound (CEUS); Microbubbles; RNA interfering; XIAP; siRNA-loaded microbubble