Citation: Dongxiao Yin, Mengjie Zhang, Jiaxin Chen, Yuanyu Huang, Dehai Liang. Shear-responsive peptide/siRNA complexes as lung-targeting gene vectors[J]. Chinese Chemical Letters, ;2021, 32(5): 1731-1736. doi: 10.1016/j.cclet.2020.12.005 shu

Shear-responsive peptide/siRNA complexes as lung-targeting gene vectors

Dongxiao Yin ^a ,
Mengjie Zhang ^b ,
Jiaxin Chen ^a ,
Yuanyu Huang ^{b, *} ,
Dehai Liang ^{a, *}

a.
Beijing National Laboratory for Molecular Sciences and the Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China
b.
School of Life Science, Advanced Research Institute of Multidisciplinary Science, Institute of Engineering Medicine, Key Laboratory of Molecular Medicine and Biotherapy, Beijing Institute of Technology, Beijing 100081, China

yyhuang@bit.edu.cn

dliang@pku.edu.cn

Received Date: 24 August 2020
Revised Date: 4 December 2020
Accepted Date: 7 December 2020
Available Online: 11 December 2020

Figures(4)

Particles administrated intravenously will pass through the pulmonary capillary network before being distributed to the body. Therefore, fabrication of vectors sensitive to blood shear and active with blood components should be a practical approach to develop lung-targeting gene carriers self-regulated by circulatory system. In this work, we designed a series of cationic peptides with the same charge density but varying hydrophobicity and capacity to form hydrogen bonds, and investigated their ability to form complexes with siRNA, the behaviours of peptide/siRNA complexes in the presence of serum under shear, and the lung-targeting efficacy of the complexes regulated by blood. The hydrophobic interaction controls the complexation between peptide and siRNA, while the hydrogen bonds are responsible for the binding of peptides to the serum components in blood. In vivo tests show that all the peptide/siRNA complexes can accumulate in lung. However, only the complexes that exhibit weak interaction with serum components and can be broken down by shear avoid the inflammation and death caused by pulmonary embolism. Moreover, the peptide with strong hydrophobicity can retain siRNA in lung without early release of the cargo. Our study provides a step toward the development of adaptive gene carriers under the regulation of circulatory system.
- Peptide,
- Gene delivery,
- Shear,
- Polyelectrolyte complexes
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