Complex Coacervation-Integrated Hybrid Nanoparticles Increasing Plasmid DNA Delivery Efficiency in Vivo

Yunfei Li, Brock Humphries, Zhishan Wang, Shuyao Lang, Xuefei Huang, Hua Xiao, Yiguo Jiang, Chengfeng Yang

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Many polycation-based gene delivery vehicles have limited in vivo transfection efficiency because of their excessive exterior positive charges and/or PEGylation, both of which could result in premature dissociation and poor cellular uptake and trafficking. Here, we reported novel hybrid PEGylated nanoparticles (HNPs) that are composed of (a) poly(ethylene glycol)-b-poly(aspartate)-adamantane (PEG-P(asp)-Ad) constituting the outer PEG layer to provide colloidal stability; (b) poly(ethylenimine)10K (PEI10K) forming complex coacervate with P(asp) as the cross-linked cage preventing premature dissociation; (c) cyclodextrin-decorated PEI10K (PEI10K-CD) forming the core with reporter plasmid DNA (pDNA). These HNPs exhibited an increased stability and higher in vitro transfection efficiency compared to traditional PEGylated nanoparticles (PEG-NP). Intratumoral injections further demonstrated that HNPs were able to successfully deliver pDNAs into tumors, while PEG-NP and PEI25K had only negligible delivery efficiencies. Moreover, HNPs' in vivo stability and pDNA delivery capability post intravenous injection were also confirmed by live animal bioluminescence and fluorescence image analysis. It is likely that the coacervation integration at the interface of PEI10K-CD/pDNA core and the PEG shell attributed to the significantly improved in vivo transfection efficiency of HNPs over PEG-NP and PEI25K. This study suggests that the HNP has the potential for in vivo gene delivery applications with significantly improved gene transfection efficiency.

Original languageEnglish
Pages (from-to)30735-30746
Number of pages12
JournalACS Applied Materials and Interfaces
Volume8
Issue number45
DOIs
StatePublished - Nov 16 2016

Bibliographical note

Funding Information:
This study was supported in part by a Research Scholar Grant (RGS-15-026-01-CSM) from American Cancer Society to C.Y.

Publisher Copyright:
© 2016 American Chemical Society.

Keywords

  • PEGylated
  • complex coacervation
  • in vivo delivery
  • plasmid DNA
  • transfection efficiency

ASJC Scopus subject areas

  • Materials Science (all)

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