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Ultrasound Responsive Magnetic Mesoporous Silica Nanoparticle-Loaded Microbubbles for Efficient Gene Delivery
ACS Biomaterials Science & Engineering ( IF 5.8 ) Pub Date : 2020-03-29 , DOI: 10.1021/acsbiomaterials.0c00014
Meng Du 1 , Yuhao Chen 1 , Jiawei Tu 1 , Chun Liufu 1 , Jinsui Yu 1 , Zhen Yuan 2 , Xiaojing Gong 3 , ZhiYi Chen 1
Affiliation  

Purpose: Gene therapy is an important therapeutic strategy for cancer. Nanoparticles are used for noninvasive gene delivery, which has great potential in tumor therapy. However, it is a challenge to construct a targeted gene delivery vector with high gene delivery efficiency, good biocompatibility, and multiple functions. Method: Herein, we designed magnetic mesoporous silica nanoparticle loading microbubbles (M-MSN@MBs) for ultrasound-mediated imaging and gene transfection. The plasmid DNA (pDNA) was encapsulated into the pores of M-MSNs. Also, the pDNA-carrying M-MSNs were loaded in the lipid microbubbles. Results: The gene vector presented good biocompatibility, DNA binding stability, ultrasound imaging performance, and magnetic responsiveness. The polyethyleneimine (PEI)-modified M-MSNs effectively protected the loaded pDNA from enzyme degradation. The cytotoxicity of M-MSNs was significantly reduced via encapsulating in lipid microbubbles. Upon the magnetic field, M-MSN@MBs were attracted to the tumor area. Then, ultrasound-targeted microbubble destruction (UTMD) not only released loaded M-MSNs but also facilitated M-MSNs delivery to tumor tissue by opening blood–tumor barrier and increasing the cytomembrane permeability, and ultimately improved the pDNA delivery efficiency. Conclusion: Our findings suggested that the developed ultrasound-responsive gene delivery system was a promising platform for gene therapy, which could noninvasively enhance tumor gene transfection.

中文翻译:

超声响应磁性介孔二氧化硅纳米粒子微气泡的高效基因传递。

目的:基因疗法是治疗癌症的重要策略。纳米颗粒用于无创基因传递,在肿瘤治疗中具有巨大潜力。然而,构建具有高基因递送效率,良好的生物相容性和多功能的靶向基因递送载体是一个挑战。方法:在本文中,我们设计了磁性介孔二氧化硅纳米粒子负载微泡(M-MSN @ MBs),用于超声介导的成像和基因转染。质粒DNA(pDNA)被封装到M-MSNs的孔中。另外,将携带pDNA的M-MSN装载在脂质微泡中。结果:该基因载体具有良好的生物相容性,DNA结合稳定性,超声成像性能和磁响应能力。聚乙烯亚胺(PEI)修饰的M-MSN可有效保护负载的pDNA免受酶降解。通过包裹在脂质微泡中,M-MSN的细胞毒性显着降低。在磁场下,M-MSN @ MBs被吸引到肿瘤区域。然后,超声靶向微泡破坏(UTMD)不仅释放了负载的M-MSN,而且还通过打开血-肿瘤屏障和增加细胞膜通透性促进了M-MSN向肿瘤组织的递送,最终提高了pDNA的递送效率。结论:我们的发现表明,开发的超声响应基因递送系统是用于基因治疗的有前途的平台,可以无创地增强肿瘤基因的转染。
更新日期:2020-03-29
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