PMID- 29360450 OWN - NLM STAT- MEDLINE DCOM- 20180222 LR - 20220331 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 496 IP - 3 DP - 2018 Feb 12 TI - Noninvasive, targeted gene therapy for acute spinal cord injury using LIFU-mediated BDNF-loaded cationic nanobubble destruction. PG - 911-920 LID - S0006-291X(18)30138-4 [pii] LID - 10.1016/j.bbrc.2018.01.123 [doi] AB - Various gene delivery systems have been widely studied for the acute spinal cord injury (SCI) treatment. In the present study, a novel type of brain-derived neurotrophic factor (BDNF)-loaded cationic nanobubbles (CNBs) conjugated with MAP-2 antibody (mAb(MAP-2)/BDNF/CNBs) was prepared to provide low-intensity focused ultrasound (LIFU)-targeted gene therapy. In vitro experiments, the ultrasound-targeted tranfection to BDNF overexpressioin in neurons and efficiently inhibition neuronal apoptosis have been demonstrated, and the elaborately designed mAb(MAP-2)/BDNF/CNBs can specifically target to the neurons. Furthermore, in a acute SCI rat model, LIFU-mediated mAb(MAP-2)/BDNF/CNBs transfection significantly increased BDNF expression, attenuated histological injury, decreased neurons loss, inhibited neuronal apoptosis in injured spinal cords, and increased BBB scores in SCI rats. LIFU-mediated mAb(MAP-2)/BDNF/CNBs destruction significantly increase transfection efficiency of BDNF gene both in vitro and in vivo, and has a significant neuroprotective effect on the injured spinal cord. Therefore, the combination of LIFU irradiation and gene therapy through mAb(MAP-2)/BDNF/CNBs can be considered as a novel non-invasive and targeted treatment for gene therapy of SCI. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Song, Zhaojun AU - Song Z AD - Department of Orthopaedics, Suining Central Hospital, Sichuan, People's Republic of China. FAU - Ye, Yongjie AU - Ye Y AD - Department of Orthopaedics, Suining Central Hospital, Sichuan, People's Republic of China. FAU - Zhang, Zhi AU - Zhang Z AD - Department of Orthopaedics, Suining Central Hospital, Sichuan, People's Republic of China. Electronic address: zhangzhispine@163.net. FAU - Shen, Jieliang AU - Shen J AD - Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China. FAU - Hu, Zhenming AU - Hu Z AD - Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China. FAU - Wang, Zhigang AU - Wang Z AD - Institution of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China. FAU - Zheng, Jiazhuang AU - Zheng J AD - Department of Orthopaedics, Suining Central Hospital, Sichuan, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180131 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cations) RN - 0 (Delayed-Action Preparations) RN - 0 (Fluorocarbons) RN - 0 (Nanocapsules) RN - 7171WSG8A2 (BDNF protein, human) RN - CK0N3WH0SR (perflutren) SB - IM MH - Acute Disease MH - Animals MH - Brain-Derived Neurotrophic Factor/*administration & dosage/genetics MH - Cations MH - Delayed-Action Preparations/*administration & dosage MH - Fluorocarbons/radiation effects MH - Gene Targeting/methods MH - Genetic Therapy/*methods MH - High-Energy Shock Waves MH - Male MH - Molecular Targeted Therapy/methods MH - Nanocapsules/chemistry/*radiation effects MH - Nanospheres/chemistry/radiation effects MH - Rats MH - Rats, Sprague-Dawley MH - Sonication/*methods MH - Spinal Cord Injuries/*genetics/pathology/*therapy MH - Treatment Outcome OTO - NOTNLM OT - BDNF OT - Cationic nanobubble OT - Gene therapy OT - LIFU OT - Spinal cord injury EDAT- 2018/01/24 06:00 MHDA- 2018/02/23 06:00 CRDT- 2018/01/24 06:00 PHST- 2018/01/17 00:00 [received] PHST- 2018/01/19 00:00 [accepted] PHST- 2018/01/24 06:00 [pubmed] PHST- 2018/02/23 06:00 [medline] PHST- 2018/01/24 06:00 [entrez] AID - S0006-291X(18)30138-4 [pii] AID - 10.1016/j.bbrc.2018.01.123 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2018 Feb 12;496(3):911-920. doi: 10.1016/j.bbrc.2018.01.123. Epub 2018 Jan 31.