Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors

Wei Li,1,2,* Huafei Li,1,* Jinfeng Li,1,* Huajing Wang,1,* He Zhao,1 Li Zhang,1 Yu Xia,1 Zengwei Ye,1 Jie Gao,1,2 Jianxin Dai,1–3 Hao Wang,1–3 Yajun Guo1–31International Joint Cancer Institute, The Second Military Medical University, Shanghai, 2National Engi...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Li W, Li H, Li J, Wang H, Zhao H, Zhang L, Xia Y, Ye Z, Gao J, Dai J, Guo Y
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2012
Materias:
Acceso en línea:https://doaj.org/article/ef3bd7520cd449cb83e189fb4c6282c7
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:ef3bd7520cd449cb83e189fb4c6282c7
record_format dspace
spelling oai:doaj.org-article:ef3bd7520cd449cb83e189fb4c6282c72021-12-02T05:09:41ZSelf-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors1176-91141178-2013https://doaj.org/article/ef3bd7520cd449cb83e189fb4c6282c72012-08-01T00:00:00Zhttp://www.dovepress.com/self-assembled-supramolecular-nano-vesicles-for-safe-and-highly-effici-a10766https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Wei Li,1,2,* Huafei Li,1,* Jinfeng Li,1,* Huajing Wang,1,* He Zhao,1 Li Zhang,1 Yu Xia,1 Zengwei Ye,1 Jie Gao,1,2 Jianxin Dai,1–3 Hao Wang,1–3 Yajun Guo1–31International Joint Cancer Institute, The Second Military Medical University, Shanghai, 2National Engineering Research Center for Antibody Medicine, State Key Laboratory of Antibody Medicine and Targeting Therapy and Shanghai Key Laboratory of Cell Engineering, Shanghai, 3PLA General Hospital Cancer Center, PLA Graduate School of Medicine, Beijing, People's Republic of China*These authors contributed equally to this workAbstract: The main obstacles for cationic polyplexes in gene delivery are in vivo instability and low solid-tumor accumulation. Safe vectors with high transfection efficiency and in vivo tumor accumulation are therefore highly desirable. In this study, the amphiphilic block copolymer poly(n-butyl methacrylate)-b-poly(N-acryloylmorpholine) was synthesized by reversible addition–fragmentation chain-transfer (RAFT) radical polymerization. The corresponding well-defined vesicles with narrow size distribution were tailored by finely regulating the packing parameter (β) of copolymer (1/2 < β < 1). Compared with traditional "gold-standard" polycation (polyethylenimine, 25 kDa), plasmid DNA condensing efficiency, DNase I degradation protection, and cellular uptake were improved by the supramolecular nano vesicles. In addition, the plasmid DNA transferring efficiency in 10% fetal bovine serum medium was enlarged five times to that of polyethylenimine in renal tubular epithelial and human hepatocellular carcinoma cell lines. This improved in vitro transfection was mainly attributed to the densely packed bilayer. This stealth polyplex showed high serum stability via entropic repulsion, which further protected the polyplex from being destroyed during sterilization. As indicated by the IVIS® Lumina II Imaging System (Caliper Life Sciences, Hopkinton, MA) 24 hours post-intravenous administration, intra-tumor accumulation of the stealth polyplex was clearly promoted. This study successfully circumvented the traditional dilemma of efficient gene transfection at a high nitrogen-from-polyethylenimine to phosphate-from-DNA ratio that is accompanied with site cytotoxicity and low stability. As such, these simply tailored non-cytotoxic nano vesicles show significant potential for use in practical gene therapy.Keywords: block copolymer, nano vesicle, gene transfection, serum stability, intra-tumor accumulationLi WLi HLi JWang HZhao HZhang LXia YYe ZGao JDai JWang HGuo YDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 4661-4677 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Li W
Li H
Li J
Wang H
Zhao H
Zhang L
Xia Y
Ye Z
Gao J
Dai J
Wang H
Guo Y
Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors
description Wei Li,1,2,* Huafei Li,1,* Jinfeng Li,1,* Huajing Wang,1,* He Zhao,1 Li Zhang,1 Yu Xia,1 Zengwei Ye,1 Jie Gao,1,2 Jianxin Dai,1–3 Hao Wang,1–3 Yajun Guo1–31International Joint Cancer Institute, The Second Military Medical University, Shanghai, 2National Engineering Research Center for Antibody Medicine, State Key Laboratory of Antibody Medicine and Targeting Therapy and Shanghai Key Laboratory of Cell Engineering, Shanghai, 3PLA General Hospital Cancer Center, PLA Graduate School of Medicine, Beijing, People's Republic of China*These authors contributed equally to this workAbstract: The main obstacles for cationic polyplexes in gene delivery are in vivo instability and low solid-tumor accumulation. Safe vectors with high transfection efficiency and in vivo tumor accumulation are therefore highly desirable. In this study, the amphiphilic block copolymer poly(n-butyl methacrylate)-b-poly(N-acryloylmorpholine) was synthesized by reversible addition–fragmentation chain-transfer (RAFT) radical polymerization. The corresponding well-defined vesicles with narrow size distribution were tailored by finely regulating the packing parameter (β) of copolymer (1/2 < β < 1). Compared with traditional "gold-standard" polycation (polyethylenimine, 25 kDa), plasmid DNA condensing efficiency, DNase I degradation protection, and cellular uptake were improved by the supramolecular nano vesicles. In addition, the plasmid DNA transferring efficiency in 10% fetal bovine serum medium was enlarged five times to that of polyethylenimine in renal tubular epithelial and human hepatocellular carcinoma cell lines. This improved in vitro transfection was mainly attributed to the densely packed bilayer. This stealth polyplex showed high serum stability via entropic repulsion, which further protected the polyplex from being destroyed during sterilization. As indicated by the IVIS® Lumina II Imaging System (Caliper Life Sciences, Hopkinton, MA) 24 hours post-intravenous administration, intra-tumor accumulation of the stealth polyplex was clearly promoted. This study successfully circumvented the traditional dilemma of efficient gene transfection at a high nitrogen-from-polyethylenimine to phosphate-from-DNA ratio that is accompanied with site cytotoxicity and low stability. As such, these simply tailored non-cytotoxic nano vesicles show significant potential for use in practical gene therapy.Keywords: block copolymer, nano vesicle, gene transfection, serum stability, intra-tumor accumulation
format article
author Li W
Li H
Li J
Wang H
Zhao H
Zhang L
Xia Y
Ye Z
Gao J
Dai J
Wang H
Guo Y
author_facet Li W
Li H
Li J
Wang H
Zhao H
Zhang L
Xia Y
Ye Z
Gao J
Dai J
Wang H
Guo Y
author_sort Li W
title Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors
title_short Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors
title_full Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors
title_fullStr Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors
title_full_unstemmed Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors
title_sort self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors
publisher Dove Medical Press
publishDate 2012
url https://doaj.org/article/ef3bd7520cd449cb83e189fb4c6282c7
work_keys_str_mv AT liw selfassembledsupramolecularnanovesiclesforsafeandhighlyefficientgenedeliverytosolidtumors
AT lih selfassembledsupramolecularnanovesiclesforsafeandhighlyefficientgenedeliverytosolidtumors
AT lij selfassembledsupramolecularnanovesiclesforsafeandhighlyefficientgenedeliverytosolidtumors
AT wangh selfassembledsupramolecularnanovesiclesforsafeandhighlyefficientgenedeliverytosolidtumors
AT zhaoh selfassembledsupramolecularnanovesiclesforsafeandhighlyefficientgenedeliverytosolidtumors
AT zhangl selfassembledsupramolecularnanovesiclesforsafeandhighlyefficientgenedeliverytosolidtumors
AT xiay selfassembledsupramolecularnanovesiclesforsafeandhighlyefficientgenedeliverytosolidtumors
AT yez selfassembledsupramolecularnanovesiclesforsafeandhighlyefficientgenedeliverytosolidtumors
AT gaoj selfassembledsupramolecularnanovesiclesforsafeandhighlyefficientgenedeliverytosolidtumors
AT daij selfassembledsupramolecularnanovesiclesforsafeandhighlyefficientgenedeliverytosolidtumors
AT wangh selfassembledsupramolecularnanovesiclesforsafeandhighlyefficientgenedeliverytosolidtumors
AT guoy selfassembledsupramolecularnanovesiclesforsafeandhighlyefficientgenedeliverytosolidtumors
_version_ 1718400567561158656