COLLOIDS AND SURFACES B-BIOINTERFACES
·
2017
·
IF 3.887
Jianwei Du,Xiao Zhao,Bangbang Li,Yun Mou,Youxiang Wang
The microbubble is a kind of clinically applied ultrasound contrast agent in disease diagnosis that can also rupture under sonication to increase membrane permeability and promote gene entry into targeted cells. However, the development of ultrasound-mediated gene delivery might be restricted because genes and microbubbles were separated and would not reach the targeted cells simultaneously. Herein, a kind of crosslinked positive microbubbles (CPMBs) were prepared to load DNA as gene vectors to promote gene delivery efficiency. The BSA shell of the CPMBs was crosslinked with disulfide bonds, which obviously enhanced the stability of the CPMBs. Furthermore, the CPMBs revealed sonoporation effects comparable to those of clinically applied SonoVue microbubbles. As DNA and CPMBs were electrostatically linked as an entirety, they would reach cells simultaneously. Thus, with the aid of ultrasound, these DNA-loaded microbubbles promoted DNA entry into cytoplasm more effectively and obtained higher cellular uptake efficiency and better transfection efficiency than DNA-mixed microbubbles. Confocal microscopy results showed that rupturing of the CPMBs/DNA entire microbubbles under sonication could carry DNA directly into the cytoplasm or nucleus. All results indicated that the cytocompatible DNA-loaded microbubbles have promising prospects in ultrasound-mediated gene delivery.
研究领域:
生物医学工程
·
基因治疗
·
超声成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
·
2015
·Vol. 15
·期 4
·2605-2612
·
IF 1.556
Lei Hulong,Nan Xiang,Wang Zhiyong,Gao Lin,Xie Lisi,Zou Chao,Wan Qian,Pan Di,Beauchamp Norman,Yang Xiaoming,Matula Thomas,Qiu Bensheng
Magnetosonoporation (MSP) is a relatively safe and efficient approach for instant MR stem cell labeling. In this study, the physical and magnetic properties of different formulations of synthesized superparamagnetic iron oxide nanoparticles (SPION) were characterized. Then, a “closed”
MSP apparatus using focused ultrasound was designed and the feasibility of MSP stem cell labelling using focused ultrasound was validated by evaluating the proliferation, migration and differentiation of the magnetically labeled cells. Subsequently, MSP/SPION labeled neural stem cells (NSCs)
were transplanted into the contralateral striatum of glioma-bearing nude mice, and their migration was monitored using magnetic resonance imaging (MRI) in vivo. The results indicated that SPION-1 with the largest size (28.43±9.55 nm) had the highest T
2 relaxivity
(136.62 Fe mM−1 S−1) and the best MRI contrast effect. Without additional transfection reagents, NSCs were labeled with SPION using focused ultrasound in vitro and the safety of MSP stem cell labeling was validated with the optimized MSP technique. Finally,
confirmed by histological evaluation, pronounced signal attenuation on T
2-weighted images demonstrated the intracranial tumor tropism of NSCs could be monitored non-invasively by MRI. In conclusion, MSP cell labeling using focused ultrasound is a promising technique and the
“closed” device is feasible, convenient and safe for instant magnetic stem cell labeling and MRI cell tracking.
研究领域:
医学影像
·
纳米技术
·
干细胞研究
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2020
·Vol. 8
·期 19
·5329-5345
·
IF 6.183
Wei Dong,Anqi Huang,Jixiu Huang,Pengying Wu,Shifang Guo,Huasheng Liu,Mengfan Qin,Xinxing Yang,Bo Zhang,Mingxi Wan,Yujin Zong
Using ultrasound activating contrast agents to induce sonoporation is a potential strategy for effective lesion-targeted gene delivery. Previous reports have proven that submicron nanodroplets have a better advantage than microbubbles in that they can pass through tumor vasculature endothelial gaps by passive targeting; however, they cannot achieve an adequate dose in tumors to facilitate ultrasound-enhanced gene delivery. Additionally, a few studies focused on delivering macromolecular genetic materials (i.e. overexpression plasmid and CRISPR plasmid) have presented more unique advantages than small-molecular genetic materials (i.e. miRNA mimics, siRNA and shRNA etc.), such as enhancing the expression of target genes with long-term effectiveness. Thereby, we constructed novel plasmid-loadable magnetic/ultrasound-responsive nanodroplets, where superparamagnetic iron oxide nanoparticle dispersed perfluoropentane was encapsulated with lipids to which plasmids could be adhered, and branched polyethylenimine was used to protect the plasmids from enzymolysis. Furthermore, in vitro and in vivo studies were performed to verify the magnetic tumor-targeting ability of the plasmid-loadable magnetic/ultrasound-responsive nanodroplets and focused ultrasound enhanced intracellular plasmid delivery. The plasmid-loadable magnetic/ultrasound-responsive nanodroplets, carrying 16–19 plasmids per droplet, had desirable diameters less than 300 nm, and integrated the merits of excellent magnetic targeting capabilities and phase transition sensitivity to focused ultrasound. Under programmable focused ultrasound exposure, the plasmid-loadable magnetic/ultrasound-responsive nanodroplets underwent a phase-transition into echogenic microbubbles and the subsequent inertial cavitation of the microbubbles achieved an ∼40% in vitro plasmid delivery efficiency. Following intravenous administration, T2-weighted magnet resonance imaging, scanning electron microscopy and inductively coupled plasma optical emission spectrometry of the tumors showed significantly enhanced intratumoral accumulation of the plasmid-loadable magnetic/ultrasound-responsive nanodroplets under an external magnetic field. And a GFP ELISA assay and immunofluorescence staining indicated that focused ultrasound-induced inertial cavitation of the plasmid-loadable magnetic/ultrasound-responsive nanodroplets significantly enhanced the intracellular delivery of plasmids within the tumor after magnet-assisted accumulation, while only lower GFP levels were observed in the tumors on applying focused ultrasound or an external magnet alone. Taken together, utilizing the excellent plasmid-loadable magnetic/ultrasound-responsive nanodroplets combined with magnetism and ultrasound could efficiently deliver plasmids to cancer cells, which could be a potential strategy for macromolecular genetic material delivery in the clinic to treat cancer.
研究领域:
生物医学工程
·
纳米技术
·
癌症治疗
·
基因递送
·
超声成像
·
磁性靶向
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）