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

doi:10.1021/acsami.6b10306

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

Markey Cancer Center / Cancer Research Priority Initiative

Research output: Contribution to journal › Article › peer-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 (PEI_10K) forming complex coacervate with P(asp) as the cross-linked cage preventing premature dissociation; (c) cyclodextrin-decorated PEI_10K (PEI_10K-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 PEI_25K 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 PEI_10K-CD/pDNA core and the PEG shell attributed to the significantly improved in vivo transfection efficiency of HNPs over PEG-NP and PEI_25K. This study suggests that the HNP has the potential for in vivo gene delivery applications with significantly improved gene transfection efficiency.

Original language	English
Pages (from-to)	30735-30746
Number of pages	12
Journal	ACS Applied Materials and Interfaces
Volume	8
Issue number	45
DOIs	https://doi.org/10.1021/acsami.6b10306
State	Published - 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)

Access to Document

10.1021/acsami.6b10306

Cite this

@article{67289b346c324caead632bc8354d7297,

title = "Complex Coacervation-Integrated Hybrid Nanoparticles Increasing Plasmid DNA Delivery Efficiency in Vivo",

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.",

keywords = "PEGylated, complex coacervation, in vivo delivery, plasmid DNA, transfection efficiency",

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

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: {\textcopyright} 2016 American Chemical Society.",

year = "2016",

month = nov,

day = "16",

doi = "10.1021/acsami.6b10306",

language = "English",

volume = "8",

pages = "30735--30746",

number = "45",

}

TY - JOUR

T1 - Complex Coacervation-Integrated Hybrid Nanoparticles Increasing Plasmid DNA Delivery Efficiency in Vivo

AU - Li, Yunfei

AU - Humphries, Brock

AU - Wang, Zhishan

AU - Lang, Shuyao

AU - Huang, Xuefei

AU - Xiao, Hua

AU - Jiang, Yiguo

AU - Yang, Chengfeng

PY - 2016/11/16

Y1 - 2016/11/16

N2 - 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.

AB - 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.

KW - PEGylated

KW - complex coacervation

KW - in vivo delivery

KW - plasmid DNA

KW - transfection efficiency

UR - http://www.scopus.com/inward/record.url?scp=84996484084&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84996484084&partnerID=8YFLogxK

U2 - 10.1021/acsami.6b10306

DO - 10.1021/acsami.6b10306

M3 - Article

C2 - 27781434

AN - SCOPUS:84996484084

VL - 8

SP - 30735

EP - 30746

IS - 45

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this