PMID- 29339208 OWN - NLM STAT- MEDLINE DCOM- 20190130 LR - 20240104 IS - 1872-7980 (Electronic) IS - 0304-3835 (Linking) VI - 418 DP - 2018 Apr 1 TI - Targeted shRNA-loaded liposome complex combined with focused ultrasound for blood brain barrier disruption and suppressing glioma growth. PG - 147-158 LID - S0304-3835(18)30057-0 [pii] LID - 10.1016/j.canlet.2018.01.035 [doi] AB - Our previous studies have demonstrated that focused ultrasound (FUS) combined with DNA-loaded microbubbles (MBs) can induce noninvasive, reversible, local disruption of the blood brain barrier (BBB) and enable targeted exogenous gene transfer into the central nervous system. However, due to low gene loading or the absence of positive targeting, to date, there has been no therapeutic effect of MBs combined with FUS in tumor treatment. In the current study, we adopted a phospholipid complex that exhibited sufficient gene loading and peptide-mediated targeting to delay glioma growth. First, we bound MBs to shBirc5-lipo-NGR, which performed the dual function of tumor cell targeting and effective gene loading. Next, we demonstrated that FUS-aided MB-shBirc5-lipo-NGR exhibited a higher transfection efficiency compared with the control group. Finally, we evaluated the silencing effect of shBirc5 using an apoptosis assay, real time-polymerase chain reaction (PCR), western blotting (WB) in vitro and a volume measurement survival analysis in vivo. The experimental group exhibited a significant therapeutic effect, while the FUS-only, MB-shBirc5-lipo-NGR-only and FUS-aided MB-shControl-lipo-NGR groups displayed no changes in tumor growth or survival time (P < .01). Consequently, our study indicated that MB-shBirc5-lipo-NGR combined with FUS is a promising new RNA interference technique for the treatment of glioma. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Zhao, Guanjian AU - Zhao G AD - Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China; Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. FAU - Huang, Qin AU - Huang Q AD - Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. FAU - Wang, Feng AU - Wang F AD - Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. FAU - Zhang, Xiang AU - Zhang X AD - Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China; Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. FAU - Hu, Jiangang AU - Hu J AD - Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China; Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. FAU - Tan, Ying AU - Tan Y AD - Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. FAU - Huang, Ning AU - Huang N AD - Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. FAU - Wang, Zhigang AU - Wang Z AD - Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. FAU - Wang, Zhibiao AU - Wang Z AD - Laboratory of Ultrasound Engineering in Medicine Co-Founded by Chongqing and the Ministry of Science and Technology, Chongqing, 400016, China. FAU - Cheng, Yuan AU - Cheng Y AD - Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. Electronic address: 646872221@qq.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180112 PL - Ireland TA - Cancer Lett JT - Cancer letters JID - 7600053 RN - 0 (Contrast Media) RN - 0 (Liposomes) RN - 0 (Oligopeptides) RN - 0 (RNA, Small Interfering) RN - 0 (Survivin) SB - IM MH - Animals MH - Blood-Brain Barrier/*metabolism MH - Brain Neoplasms/genetics/metabolism/*therapy MH - Cell Line, Tumor MH - Contrast Media/chemistry MH - Drug Delivery Systems/methods MH - Genetic Therapy/methods MH - Glioma/genetics/metabolism/*therapy MH - Liposomes/*chemistry MH - Microbubbles MH - Oligopeptides/genetics MH - RNA, Small Interfering/administration & dosage/chemistry/*genetics MH - Rats MH - Sonication/*methods MH - Survivin/genetics MH - Treatment Outcome OTO - NOTNLM OT - FUS OT - Glioma OT - Liposome complex OT - Targeted gene therapy OT - shRNA EDAT- 2018/01/18 06:00 MHDA- 2019/01/31 06:00 CRDT- 2018/01/18 06:00 PHST- 2017/08/11 00:00 [received] PHST- 2017/12/23 00:00 [revised] PHST- 2018/01/09 00:00 [accepted] PHST- 2018/01/18 06:00 [pubmed] PHST- 2019/01/31 06:00 [medline] PHST- 2018/01/18 06:00 [entrez] AID - S0304-3835(18)30057-0 [pii] AID - 10.1016/j.canlet.2018.01.035 [doi] PST - ppublish SO - Cancer Lett. 2018 Apr 1;418:147-158. doi: 10.1016/j.canlet.2018.01.035. Epub 2018 Jan 12.