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Prussian blue nanoparticle-loaded microbubbles for photothermally enhanced gene delivery through ultrasound-targeted microbubble destruction

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  • Materials Science
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Abstract

By adsorbing chitosan (CS)-functionalized Prussian blue (PB) nanoparticles (CS/PB NPs) complexing DNA onto the surface of gas encapsulated microbubbles (MBs), a multifunctional gene delivery system of MBs@CS/PB/DNA was fabricated for photothermally enhanced gene transfection through ultrasound-targeted microbubble destruction. CS/PB NPs of (2.69 ± 0.49) nm could complex DNA effectively when the mass ratio was 2:1. It was found that MBs@CS/PB/DNA could enhance ultrasound imaging greatly both in vitro and in vivo. In addition, MBs@CS/PB/DNA could be disrupted by applying a higher-intensity ultrasound irradiation to release CS/PB/DNA, which could effectively transform the near-infrared (NIR) light into heat to assist the uptake of CS/PB/DNA by cells. With the aid of ultrasound irradiation and NIR light irradiation, the gene transfection efficiency was significantly enhanced to (43.08 ± 1.13) %, much higher than polyethylenimine. Moreover, MBs@CS/PB/DNA showed excellent biocompatibility, encouraging the further exploration of MBs@CS/PB/DNA to be a platform for combined ultrasound image, photothermal therapy, drug delivery, and gene therapy.

摘要

使用壳聚糖修饰普鲁士蓝纳米粒子吸附DNA,再将其复合物吸附到超声微泡的表面,构成可以联合超声破碎和光热作用来共同提高基因转染效率的声光控基因转染平台。制备的壳聚糖修饰普鲁士蓝纳米粒子粒径约为2 nm,可以高效吸附DNA,其复合物吸附到超声微泡表面后构成了普鲁士蓝微泡。超声成像实验结果表明,该微泡可以显著提高超声成像效果。通过对普鲁士蓝微泡进行高强度超声辐照,可以破碎超声微泡,释放出壳聚糖修饰普鲁士蓝纳米粒子与DNA的复合物。再对该复合物进行近红外光照射,可以显著提高细胞对壳聚糖修饰普鲁士蓝纳米粒子与DNA复合物的摄取,从而提高基因转染效率。体外和体内实验验证了普鲁士蓝微泡具有很好的生物安全性,因此将普鲁士蓝微泡用于超声造影成像、光热治疗和基因治疗等方面都具有很好的应用前景。

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (81371580 and 21273014), the National Natural Science Foundation for Distinguished Young Scholars (81225011) and the State Key Program of National Natural Science of China (81230036).

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Authors and Affiliations

  1. School of Municipal and Environmental Engineering, School of Life Science and Technology, Harbin Institute of Technology, Harbin, 150080, China

    Xiaoda Li, Xiuli Yue, Lijia Jing, Li Lin, Yongbo Yang & Shanshan Feng

  2. College of Engineering, Peking University Third Hospital, Peking University, Beijing, 100871, China

    Jinrui Wang, Xiaolong Liang, Yajun Qian & Zhifei Dai

Authors
  1. Xiaoda Li
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  2. Xiuli Yue
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  3. Jinrui Wang
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  4. Xiaolong Liang
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  5. Lijia Jing
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  6. Li Lin
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  7. Yongbo Yang
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  8. Shanshan Feng
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  9. Yajun Qian
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  10. Zhifei Dai
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Correspondence to Xiuli Yue.

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Li, X., Yue, X., Wang, J. et al. Prussian blue nanoparticle-loaded microbubbles for photothermally enhanced gene delivery through ultrasound-targeted microbubble destruction. Sci. Bull. 61, 148–156 (2016). https://doi.org/10.1007/s11434-015-0988-4

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  • DOI: https://doi.org/10.1007/s11434-015-0988-4

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