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Bioreducible Polyspermine-Based Gene Carriers for Efficient siRNA Delivery: Effects of PEG Conjugation on Gene Silencing Efficiency

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Abstract

A polyspermine-derived bioreducible polymer was synthesized as efficient siRNA carriers. Spermine was polymerized using disulfide-bearing cross-linkers, resulting in poly(disulfide spermine) (PDS). PDS was also conjugated with poly(ethylene glycol) (PEG) to tailor siRNA condensation efficiency of the polymer. PEG-conjugated PDS (PEG-PDS) was able to condense siRNA into nano-sized polyplexes at high N/P ratios. siRNA condensation efficiency of PDS was reduced by PEGylation due to its weakened interaction with siRNA caused by its decreased cationic charge density. An ethidium bromide exclusion assay demonstrated that siRNA was more efficiently released from the less stable PEG-PDS polyplexes compared to stable PDS polyplexes. In addition, bioreducible siRNA/PEG-PDS polyplexes were efficiently disassembled in the reductive conditions, leading to facilitated siRNA release into the cytoplasm. The lowered siRNA condensation but efficient cytoplasmic release of siRNA by PEG-PDS induced higher gene silencing efficiency in comparison with PDS. Moreover, PEG-PDS exhibited lower cytotoxicity compared to PDS and non-biodegradable branched polyethylenimine. These results suggest that siRNA delivery efficiency of cationic gene carriers can be improved by tailoring their siRNA complexation through PEG conjugation. This study demonstrates that bioreducible PEG-PDS is a promising candidate for safe and efficient siRNA delivery.

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Authors and Affiliations

  1. School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, Korea

    Suk Ho Bhang

  2. Electrochemistry Laboratory for Sensors & Energy (ELSE), Department of Chemistry, Incheon National University, Incheon, 22012, Korea

    Kyuwon Kim

  3. Division of Bioengineering, Incheon National University, Incheon, 22012, Korea

    Won Jong Rhee & Min Suk Shim

Authors
  1. Suk Ho Bhang
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  2. Kyuwon Kim
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  3. Won Jong Rhee
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  4. Min Suk Shim
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Corresponding author

Correspondence to Min Suk Shim.

Additional information

Acknowledgments: The authors acknowledge the financial support of Convergence Research Program (2014) through Incheon National University.

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Bhang, S.H., Kim, K., Rhee, W.J. et al. Bioreducible Polyspermine-Based Gene Carriers for Efficient siRNA Delivery: Effects of PEG Conjugation on Gene Silencing Efficiency. Macromol. Res. 26, 1135–1142 (2018). https://doi.org/10.1007/s13233-019-7027-2

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  • DOI: https://doi.org/10.1007/s13233-019-7027-2

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