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PEGylated gene carriers in serum under shear flow

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The behaviour of drug/gene carriers in the blood stream under shear is still a puzzle. In this work, using the complexes formed by 21 bp DNA and poly(ethylene glycol)-b-poly(L-lysine) (PEG–PLL) of varying PEG lengths, we studied the dynamic behaviour of the complexes in the presence of fetal bovine serum (FBS) and under flow at different shear rates, a condition mimicking the internal physical environment of blood vessels. The PEG5k-PLL/DNA complex possesses a dense DNA/PLL core and a loose PEG5k protecting layer. The PEGylated DNA complexes exhibit multiple responses to external shear in the presence of FBS. The loose PEG5k layer is firstly disturbed at a shear rate below 30 s−1. The exposure of the charged core to the environment results in a secondary aggregation of the complex with FBS. The size of the aggregate is limited to a certain range as the shear rate increases to 50 s−1. The dense DNA/PLL core starts to withstand the shear force as the shear rate reaches 500 s−1. The reorganization of the core to accommodate more serum molecules leads to tertiary aggregation of the complexes. If PEG cannot form a valid layer around the complex, as in PEG2k-PLL/DNA, the complex forms an aggregate even without shear, and the first shear dependent region is missing. If the PEG layer is too stable around the complex, as in PEG10k-PLL/DNA, no tertiary aggregation occurs. The mechanism of shear on the behaviour of delivery particles in serum helps to design gene carriers with high efficacy.

Graphical abstract: PEGylated gene carriers in serum under shear flow

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Article information

05 Dec 2019
19 Jan 2020
First published
20 Jan 2020

Soft Matter, 2020, Advance Article
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PEGylated gene carriers in serum under shear flow

D. Yin, H. Wen, G. Wu, S. Li, C. Liu, H. Lu and D. Liang, Soft Matter, 2020, Advance Article , DOI: 10.1039/C9SM02397F

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